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Joan Greeley



Our bodies are made of water
The renowned Eclectic physician John Scudder calls us to notice the powerful subtleties of our bodies workings:
There is, says Dr. Williams (Principles of Medicine, p.38), in organized beings a certain conservative
power which opposes the operation of noxious agents, and labors to expel them when they are
introduced. The existence of this power has long been recognized, and in former days it was
impersonated. It was the archaeus of Van Helmont; the anima of Stahl; the vis medicatrix naturae of
Cullen. But without supposing it to be aught distinct from the ordinary attributes of living matter, we see
its frequent operation in the common performance of excretion; in the careful manner in which noxious
products of the body, and offending substances in food, are ejected from the system; in the flow of tears
to wash a grain of dust from the eye; in the act of coughing and sneezing to discharge irritating matters
from the air-passages, and in the slower, more complicated, but not less obvious example of
inflammation, effusion of lymph and suppuration, by which a thorn or other extraneous object is
removed from the flesh. (1898, pp. 48-9)
Physiomedical Therapeutics professor T.J. Lyle speaks of such subtleties when he names the four nutritious
fluids in the body. Two of them are components of the lymphatic system (chyle and lymph), and one of them is
directly influenced by the lymphatic system (blood) (1932). Two thirds of your bodily water is contained within
your cells. Of the remaining third, only 25% is in the blood plasma. While we commonly conceive of blood
volume and pressure as essential measures of wellness, less attention is given to extracellular fluid volume or
the lymph flow that regulates it. However, a significant portion of the water that is you is contained within the
lymph. The majority (75%) of extracellular fluid exists in the interstitial spaces (Silverthorn, 2009). This
interstitial fluid (IF) is literally an internal sea, a contiguous and interconnected unit in which all our tissues are
bathed, only its a sea given structure by the extracellular matrix (ECM) and drained by the lymphatic system.
The ECM IF, often referred to as ground substance (Foldi & Foldi, 2006; Pischinger, 2007), forms a
macromolecular network which enables the unhindered flow of interstitial fluid between the terminal blood
vessels and the initial lymph vessels (Foldi & Foldi, 2006, p. 155). Ground substance, however, does have a
fairly viscous consistency that changes composition and influences the rigidity of tissues and therefore the rate
of diffusion through them (Foldi & Foldi, 2006). This is at least partially due to the polarity of the proteoglycans
(PGs) and glycosaminoglycans (GAGs) that comprise the channels in the ground substance through which both
hydrophilic and lipophilic substances are transported (Pischinger, 2007). PGs and GAGs are both capable of
influencing the migration of cells through the ground substance (Foldi & Foldi, 2006).
When the body is functioning optimally, arterial filtration is greater than venous absorption so that fluid and
proteins can exit arterioles and precipitate out through capillary beds into the interstitial space (Silverthorn,

2009). One of the many essential functions the lymphatic system serves is absorbing this extra fluid from the
interstitia and returning it to systemic circulation. Yet, when the feather-shaped proteoglycans of the ECM are
forced to function in a state of reduced hydration, their fans collapse and the ECM ability to function as an
essential transfer medium is compromised (Pischinger, 2007). Pathological conditions of the lymphatic system
(lymphaedema, elephantiasis, and others) are primarily associated with this form of stasis and lack of tone (Foldi
& Foldi, 2006). Though, unfortunately, little research in the United States has been done on pre-pathological
Austrian anatomy researcher Alfred Pischingers work helps provide some context in which the pre-cursors to
such pathologies may occur. He proposes that viewing disease states in the body from a purely cellular
perspective is analogous to attempting to understand the nature of a wave by examining only one point.
Instead, his view encompasses the dynamic nature of the living system in which all physiological processes must
occur. Pischinger and colleagues state that the cell is only one part of the smallest functional common
denominator of *vertebrate+ life that forms a functional triad/unit only when viewed in conjunction with the
capillaries and extracellular matrix (Pischinger, 2007, p. 7). This viewpoint dethrones cell theory and unites us
with the classical Galenical model where disease was seen to result from an altered balance of bodily fluids
(humors). As described by Felter, this bad blood or blood dyscrasia has, as a rule, little relation to the blood
itself, but pertains chiefly to imperfect lymphatic elimination and faulty retrograde metamorphosis (Felter,
1922, p. 239). One of the essential roles of Pischingers extracellular matrix in (pre)disease processes is that of a
storehouse for toxins of all kinds. In his view, environmental, dietary, and emotional (i.e. stress) byproducts
become bound to the ECM, and, while they may not lead to immediate gross pathology, cause a maladaptation
phase of matrix regulation, a sort of cesspool of allopathic load, under which the body operates for many years
until which time as a tipping point may appear in the form of gross morbidity (Pischinger, 2007, p. 17).

The neuropeptide and cytokine milieu of the ground substance in which immune cells exist induces context-
driven differences in their function. For instance, background concentration dynamics of these inputs direct T-
cell receptor binding and influence T-cell activation or suppression; the same neurotransmitter can even induce
opposite effects depending on the background milieu (Levite, 2008). In lymph node & Peyers patch high
endothelial venules (HEV see below), GPCRs on collagen bind paracrine chemokines that direct lymphocyte
movement, and so form a stabilizing and directional link between endothelial cells and extravasating
lymphocytes in the face of lymph flow (Yang, et al., 2007). Collagen is also a key ECM component (Foldi & Foldi,
2006) to which normal epithelial cells must adhere in order to acquire adequate nutrition, energy, and
protection from damaging reactive oxygen species (ROS) (Grassian, Coloff, & Brugge, 2011). Thus, the abilities

of the ECM to release and the lymphatic circulation to clear immune cells and wastes to nodes and beyond are
essential to maintaining wellness.

In further support of Pischingers position, primate studies by Sloan and colleagues show that chronic emotional
stress increases catecholaminergic innervations of lymph nodes and other lymphoid tissues. This alters their
expression of cytokines, while chronic inflammation and aging induce denervation (Sloan, Capitanio, & Cole,
2008). The study authors suggest that these changes impose a long-term bias on immune response and
sensitize immunobiology to social and ecological conditions (2008, p. 12). One direct observation of pathology
induced by stress-driven increases in nodal innervations is the increased replication of simian immunodeficiency
virus (SIV) in stressed individuals (Sloan, Tarara, Capitanio, & Cole, 2006).

Masaru Emotos controversial and inspiring water crystal studies suggest that our intentions and emotions
influence the shape of the water around, and presumably within, us, possibly further influencing fluid dynamics
in the body. Pischingers observations echo this thought: Since psychic stress can also lead to an increase in
free radicals in the extracellular matrix, burdensome spiritual-psychic situations add to the stress load of the
body (2007, p. 17). The extracellular matrix is innervated and awash with neural (Pischinger, 2007) and other
inputs known to influence immunodynamics. The very act of breathing, and the rate and depth at which
inspirations and exhalations occur influences the rate and flow at which lymphatic fluid is moved.
Lemole elucidates:
Fluid in the thoracic duct is pumped along by the breath. A bellows mechanism, breathing exerts both a
positive and a negative pressure. If you take a deep breath and exhale deeply, you're massaging the
thoracic duct upward into the neck so that the fluid flows generously. This duct empties the lymph into
the veins, where it becomes part of the blood's plasma. From there the lymph returns to the liver for
metabolization, and finally to the kidneys for filtering." (2001, p. 20)
Taking in breath causes lymphatic flow to increase. In a way, this intimate act of inviting part of the outside
world into your being, this air, not normally conceived of as you, is inherently cleansing and renewing. It is by
ingesting this substance that you encourage your body to push out (out of interstitial space and into lymph, out
of the lymph through blood towards excretory organs) the waste products it no longer needs. Another method
for encouraging lymph flow is physical exercise, the active form of extending yourself outward into the world.
Movement in this way encourages lymphatic circulation because it gets your blood pumping, so the lymph
system has to work harder to mediate fluid balance, and because it also invites you to breathe deeply and
repeatedly. The final means for encouraging lymphatic flow is via massage, a very direct and physical interaction

with that which is not self, another human being. Lymph does not move well when youre sitting alone in your
room, breathing shallowly with worry. Lymph flows well when youre engaging with life.
"It is doubtless true that temperament exercises a great and important influence over the action of medicines;
persons of a lymphatic temperament will generally require increased quantities of all remedies to produce a
certain effect." (Scudder, 1898, p. 88) Here, Scudder introduces the idea of conditions of lymphatic
temperament, characterized by cold, damp, sluggish, slow, and melancholic tendencies (Tuke, 1892; Scudder,
1895), suggesting the use of warming, uplifting, stimulating, and moving to countermeasures to restore balance
to the system. This rhythmicity and movement is implicit in life. Like most processes in the corporeal and
universal body, lymphatic function is driven by larger rhythms, even within lymph nodes where differential
patterns of T-cell expression are influenced by circadian rhythm-driven clock genes (Fortier, Rooney, Hardy,
Labrecque, & Cermakian, 2011). It is necessary to understand what the lymphatic system does before
determining what a lymphatic herb does. So, let us now look at the physiology of the lymphatic system.
Organization of lymphatic tissues in the body
Lymphatic tissues in the body are categorized into primary and secondary lymphatic organs (SLO). The
primary lymphatic organs are the bone marrow and thymus. In the bone marrow, B lymphocytes are born and
aged. However, it is later in the SLO after encountering antigen that they acquire maturity. NK cells also
develop in the bone marrow (Foldi & Foldi, 2006). Newly born T lymphocytes leave the bone marrow to mature
in the thymus. Once mature, they venture out and settle in T-cell regions of secondary lymphoid tissues to help
direct cell-mediated immune response (Foldi & Foldi, 2006). Secondary lymphatic organs include the spleen,
mucosa-associated lymphatic tissue (see MALT below), lymph nodes, and lymph vascular system. With the
exception of the spleen, this discussion will focus largely on the secondary lymphatic organs.
Major roles of lymph in the body
Lymphatic vessels are key regulators of inflammation and fluid and lipid balance, while lymph nodes are
essential organizers of immune response, particularly humoral. The lymphatic system acts as the physical basis
of the immune system by providing the structures and tools with which to rid ourselves of that which would do
us harm (von der Weid & Rainey, 2010, p. 698). Byproducts of normal and pathophysiological processes, our
environment, and our emotions are swept out of cells and into the interstitial fluid where they are bound by
extracellular matrix components. Examples of this include the deposition of emotional stress-induced free
radicals into the ground substance and the deposition and subsequent enzymatic degradation of vesicles from

connective and immune cell tissue, both of which influence the allostatic balance of the interstitial environment
(Pischinger, 2007). Lipoproteins and cytokines are a few of the many proteins that make up the systemic lymph
fluid, with additional organ-specific components present in individual regions (extra fat in the small intestine,
hyaluronic acid in the skin, and toxins and microorganisms at sites of infection or injury, for instance). Since
blood plasma proteins cannot re-enter the bloodstream through post-capillary venules (due to concentration
gradient dynamics), they precipitate out into the interstitial space. Deposition of proteins, fats, and fluids into
the interstitial space is a means for making them and the molecules they carry accessible to local cells for uptake
(Foldi & Foldi, 2006). Anything not entering a cell, returning immediately to venous circulation, or adhering to
the ECM is invited into lymphatic precollecting capillaries and absorbed into lymph flow where it is either
phagocytized in nodes (Roozendaal, Mebius, & Kraal, 2008) or detoxified or recycled by the various structures
through which that flow eventually carries it: lymph nodes, liver, kidneys, skin, lungs, and large intestine (von
der Weid & Rainey, 2010).
Lymph vessels provide a route for dietary fats to be absorbed, stored, and metabolized. Theyre also responsible
for uptake of fat-soluble vitamins, which are absorbed into chylomicrons then enter the systemic circulatory
system (von der Weid & Rainey, 2010). Lymphatic absorption also plays an essential role in the systemic
bioavailability of insulin and other subcutaneously injected drugs (Charman, McLennan, Edwards, & Porter,
Lymphatic vasculature is the key regulator of fluid balance in the body
Lymph flow is one-way, however its nonlinear, being instead an interconnected system more weblike than
linear (Foldi & Foldi, 2006). Afferent flow brings fluid from tissues to nodes. Efferent flow moves lymph
fluid to and between nodes further along the web, towards the left subclavian vein (which drains 3/4 of the
body) or the right subclavian vein (which drains 1/4 of the body). Multiple afferent vessels enter one node, but
theres a single efferent vessel for all lymph exiting each node. The lymphatic vascular system contains both
superficial and deep sections, each with their own slightly different rhythm and morphology. Typically, lymph
moves from deep to surface vessels. The superficial vessels drain the skin and subcutis, while the deep move
lymph from the muscles, joints, tendons, and nerves. Organs are drained by organ-specific lymphatic
arrangements (Foldi & Foldi, 2006).
The lymphatic vasculature is organized into initial capillary precollectors, and then vessels of increasingly larger
size. Lymphatic vessels are organized into functional units called lymphangions which are equipped with one-
way valves to prevent backflow (Foldi & Foldi, 2006).

The lymphatic vasculature shares some similarities with blood vasculature. The principal difference is that the
endothelial cells of lymphatic primary collecting vessels dont have a basement membrane or musculature. They
do have a characteristic and structurally important oak leaf-shaped overlapping morphology (Foldi & Foldi,
2006). However, without a basement membrane to enclose them, lymph capillaries are, quite literally, awash in
a sea of interstitial fluid, surrounded by collagens, proteoglycans, fibronectin, and other extracellular matrix
components, so that interstitial pressure outside of a certain window will change lymph flow dynamics (Mallick
& Bodenham, 2003). Thus, the interstitial matrix and fluid constitute the principal microenvironment of
lymphatic tissues (Paupert, Sounni, & Noel, 2011). Proteoglycans, whose structure resembles feathers, form the
filling around the collagen- & elastin-based scaffolding of the ECM. They function to help maintain tissue
regulation of water balance, influence the interactions of fibrils with ECM components, affect the migration of
cells within the ECM matrix, and bind to a number of growth factors (Kim, et al., 2010; Foldi & Foldi, 2006).
Lymph collectors are connected to the ECM by connective tissue anchoring filaments called fibrils. Fibrils are
responsible for opening and closing lymphatic capillary precollectors via an intracellular fibrin-mediated
signaling. This cascade is initiated when the amount of interstitial fluid increases or decreases (Dieter, Dieter, &
Dieter, 2011) and causes fibrils to pull apart the top oak leaf flap of capillary endothelia leaving a gap into which
fluid can pass. This lymph vessel-ECM interplay permits the lymphatic vasculature to drain away excess fluid and
waste products in the face of tissue injury, inflammation, or tumor growth (Dieter, et al., 2011; Paupert, et al.,
2011). Because physical room to move is inherent in the pulling open of capillary oak-leaf flaps, ECM density or
laxity affects the collecting vessels ability to open and admit fluid. Lymph vessels filter plasma proteins from
the interstitial fluid. This is essential in preventing disruption of concentration gradients. If proper lymph flow
doesnt remove proteins from the IF, blood capillaries become leakier and additional fluid and proteins build up
in the IF. Inflammation and oedema may result (Silverthorn, 2009).
Lymph vessels, unlike collectors, contain a basement membrane, smooth muscle cells (SMC), and some skeletal
muscle cells, and are innervated (Foldi & Foldi, 2006; Dieter, et al., 2011). These vessels regulate systemwide
fluid dynamics. Lymphatic flow occurs in a pulsatile fashion mediated by changes in muscular polarity. Many
chemical (such as NO, discussed below) and mechanical inputs can influence both their frequency and strength
(von der Weid & Muthuchamy, 2010). Lymph flow works with bloodstream to balance blood pressure and fluid
balance, with lymphatic vessels acting as safety valves to compensate for excess interstitial fluid volume in cases
of venous insufficiency. They can increase flow volume to drain faster in this instance, thus preventing edema.
However, when lymphangion valves are dysfunctional, oedema and reduced lymph flow result (Foldi & Foldi,

The lymphatic vasculature assists in mitigating pathophysiological changes. Lymphatic endothelia derive from
venous and connective tissue precursors (Dieter, et al., 2011), this may be one reason both veins and lymphatic
vessels express receptors for vascular endothelial growth factors (VEGFR) and respond to these growth factors
in similar settings, such as conditions of tumorogenesis (Dieter,, 2011; Ji, 2007) VEGF-A, -C, -D, once
thought to only affect blood vessels, are now known to induce lymphangiogenesis as well. This lymph vessel
growth helps provide a means for wounds to heal and swollen areas to drain (Greco, Lara, Oliveira-Filho, Greco,
& Sudo-Hayashi, 2006).

Lymphatic flow also adjusts in traumatic events, such as shock, in order to restore blood volume. After burn
injury, lymph flow both clears out excess fluid from and delivers hyaluronan (aka HA or hyaluronic acid) to the
burn site. Hyaluronan, an essential component for rebuilding the interstitial matrix, helps direct fluid dynamics
and regulate cell activity during healing & inflammation (See discussion of inflammation below) (Mallick &
Bodenham, 2003). In traumas requiring surgery, local and general anesthetic administration reduces lymph flow
(Mallick & Bodenham, 2003). Oral administration of Bupleurum falcatum and Panax ginseng to rats seem to
increase in vitro lymphatic contraction in vivo lymph flow, though the mechanism for these actions is unclear
(Yamakage, Hattori, Satoh, & Namiki, 2006). Regardless, the presentation of the preceding events in a client
history could be an indication for the use of lymphagogue therapies.
Innervation of lymphatic tissues
All primary and secondary lymphoid tissues are sympathetically innervated (Sloan, Capitanio, Tarara, & Cole,
2008), and both parasympathetic and sympathetic nerve fibers exist in lymph collecting vessels (von der Weid &
Rainey, 2010). A number of neurotransmitters with broad-reaching effects have been found in lymph organs
thus far (see table 1). VIP and serotonin are two that influence vessel physiology. VIP has a relaxing effect on
lymphatic SMC (Foldi & Foldi, 2006) and promotes Th2 cell expression while suppressing Th1 cell development
(Shepherd, Downing, & Miyan, 2005). Serotonin 5-HT has been shown to increase lymph flow (Shepherd,
Downing, & Miyan, 2005), though it appears to have a broader overall regulatory effect: serotonin relaxes lymph
vessel contractions that are too tight and tones normal ones by activating different vessel 5-HT receptors (von
der Weid & Muthuchamy, 2010). It is interesting to contemplate the connections between the tendencies of
the melancholic/lymphatic temperament, modern concepts of serotonin in depression, and the 5-HT influence
on literally getting things moving smoothly in the lymph.
Social stress in primates increases neural stimulation of lymph organs, with demonstrable increases in lymph
node NGF believed to be one cause of the viral upregulation (Sloan, Tarara, Capitanio, & Cole, 2006). The ECM

itself contains innumerable cytokines, immune cells, & other mediators, and is also innervated. Importantly,
ECM interstitial fluid is where neurotransmitters are released. They dont, however, go directly from neuron to
cell; they have to diffuse across the interstitial fluid in order to reach their target tissues (Silverthorn, 2009;
Pischinger, 2007). This invites the possibility that an imbalance in ground substance composition can impede
neural signaling (Pischinger, 2007).
Not only is ground substance awash in neurotransmitters; lymph nodes are innervated, too, right up to the B-
and T-cell follicles in the nodal cortices (Shepherd, et al., 2005). Interestingly, primate studies showed that
individuals manifesting low sociability personalities had substantially greater sympathetic innervation of their
lymph nodes than did those ranking high sociability personalities, particularly in the paracortical T-cell region
(probably due to their increased levels of NGF). Functionally, this upregulation correlated with a reduction in
the overall equilibrium of Th1/Th2 immunomodulatory signaling in low sociability individuals (as a measure of IF-
and IL4) and a long-term reduction in vaccine responsiveness. These so-called low-sociable individuals have
also been observed to have increased susceptibility to a number of diseases including viral infections, atopic
allergy, and delayed-type hypersensitivity (Sloan, et al., 2008). Foldi implicates lymph nodes as veritable
breeding grounds for viruses (2006, p. 207), and catecholaminergic innervation of lymphoid tissue is implicated
in viral infections with an affinity for lymph tissue, such as HIV (Sloan, et al., 2008). These observations help us
to understand why Shepard et al. suggest that sympathetic leucocytosis can be thought of as a less-recognized
facet of the fight-or-flight response (2005, p. 152).
And, it may be a lasting effect. Innervation of lymph nodes increases upon antigenic challenge, with murine
studies suggesting that in addition to the immunological memory created by antigen challenge, there may be a
neural memory component created as well which is essential for mounting a proper memory response upon
rechallenge by that same antigen (Shepherd, et al., 2005). It is suggested that the mechanism for this neural
sensing of immune challenge is a frequency of nerve potentials produced by the membrane changes in antigen-
presenting cells responding to antigen. This unique signature is then rapidly detected by a sensory nerve which
initiates cytokine and other activity in lymphoid tissues (Shepherd, et al., 2005). In other words, the nervous
system senses antigen exposure/danger to the organism and helps to elicit an immune response in the face of
this challenge and then recalls the signal when it encounters it again. This may be especially relevant in terms of
T-cell-driven immune responses (such as virus and tumor migration and cytokine production), since T-cell
regions in nodes are the areas where stress-induced increases in innervations occur, and DC presentation of
antigens also increases under stress (Sloan, Capitanio, & Cole, 2008).


Table 1. Nervous system influences on the lymphatic system
Source Target/Role
Substance P macrophages, granulocytes,
lymphocytes, CNS c-fibers
increases lymphocyte output from lymph nodes,
mesenteric lymphatic vessel constriction
Vasoactive intestinal
peptide (VIP)
CNS/PNS nerve terminals &
lymphoid organs
Released by sensory nerves upon
damage/inflammation. Receptors on T cells,
macrophages, lymph vessels
Neuropeptide Y CNS/PNS nerve terminals, lymphoid
organs, lymphocytes, monocytes
Post-inflammation release from sympathetic terminals
w/ norepinephrine
Somatostatin CNS/PNS nerve terminals, lymphoid
Lymphocyte receptors, induce t-cell adhesion to
fibronectin, directly stimulate T-cell cytokine secretion.
Enhance or reduce lymphocyte proliferation
GNRH-I, -II T lymphocytes Affects T-cell laminin receptor, believed to facilitate T-
cell extravasation & promote memory T-cells in areas
of challenge
Serotonin 5-HT Afferent nociceptors, stored by
Proinflammatory vasodilator. Noradrenergic termini in
lymphoid organs may take up 5-HT for later release,
mediates lymph vessel tone
Epinephrine &
Lymphocytes, macrophages,
sympathetic nurons, adrenals
Inhibit IL-12 secretion by DC & therefore Th1
development, decrease proinflammatory cytokine
expression, promote anti-inflammatory cytokine
production, possible immunoactivator
Histamine Dendritic cells, T cells, Mast cells,
Potent vasodilator, activates submucosal neurons,
increases IL-10, inhibits IL-12 secretion by DC & Th1
development. Histamine receptors on DC, neurons,
endothelia, B cells, T cells, Th1 cells, main mediator of
increased lymph pumping due to mast cell activation
Melatonin Nervous & immune systems Modulates lymphocyte proliferation & Th1/Th2
cytokine balance
Adapted from Shepherd, Downing, & Miyan, 2005 and von der Weid & Muthuchamy 2010
Lymph nodes are essential organizers of immunity
There are 600-700 nodes in the body, ranging in size from 0.2 to 3cm, (Foldi & Foldi, 2006). Each node is
organized into highly specialized functional regions. Distinctive zones house T-cell or B-cell-rich cortices. Lymph
flows parallel alongside a vein & artery with its own intra-nodal capillary exchange in the cortical (B-cell) and
paracortical (T-cell) zones. The T-cell regions high-endothelial venules (HEV) provide a means for activated
lymphocytes (such as antibodies) to recirculate directly into the bloodstream (Foldi & Foldi, 2006).
Afferent flow carries fluid and antigens from the ground substance surrounding the tissues into nodes where it
empties out into the subcapsular (marginal) sinus area which extends beneath the nodes outer membrane and
then branches like spokes on a wheel (radial sinus) into the inner nodal regions of the medullary sinus (Foldi &
Foldi, 2006). It is in the marginal sinus where many macrophages wait to filter larger molecules and particles -
such as pathogens - from the incoming lymph (Roozendaal, Mebius, & Kraal, 2008). Once antigens are filtered

out, macrophages then deliver them across the inner sinus membrane to the nearby inner cortex of the node
where B-cell complement receptors capture the antigen complexes & deliver them to dendritic cells (DC) waiting
in B-cell follicles. These cognate B-cells then migrate to the paracortical T-cell region of the node. Entry
level/subcapsular macrophages appear to be only moderately phagocytic yet become opsonized for hours, while
macrophages in the (inner) medulla seem to be more heavily phagocytic (Phan, Grigorova, Okada, & Cyster,
2007). These same authors also noted that immune complexes and molecules larger than antibodies do not
readily gain free access to follicles and will typically be transported by cells (2007, p. 997).
Immune cell migration is not the only controlled movement within a node. After it enters the sinus, fluid does
not flow freely through a node. It gains entry only through small tubules originating between the sinus-lining
cells which extend from the sinus throughout the nodal B- & T-cell regions, ending at the high endothelial
venules (Roozendaal, Mebius, & Kraal, 2008, p. 1484). DCs sample at openings along the tubules, extracting
antigen they find within its flow. The fibroblastic reticular cells (FRC) that form these tubules also secrete
chemokines which attract T- and other lymphocytes that patrol along the tubal perimeter, primed and ready for
DCs to present them with antigen (Roozendaal, et al., 2008). Amazingly, within lymph nodes, the extracellular
matrix (complete with GAG, fibrillins, collagen, etc.) is internalized; it is contained within the tubules, sheathed
by the collagen fibers of a basement membrane (Roozendaal, et al., 2008). This is the opposite of what occurs
in most tissues where the extracellular matrix is, well, extracellular, outside of the cells and un-membraned.
This also means that outside of the nodal tubules, essentially no fluid exists in the node, its simply elbow-to-
elbow lymphocytes which appear only to move when FRC chemokines tell them to (Roozendaal, et al., 2008).
Tubules also connect the sinus with B cell regions. Whether an antigen gains access to the B cell cortex is
thought to be a function of the size of the antigen, with some traveling intra-tubularly and others migrating
across the sinus attached to macrophages (Phan, et al., 2007)
Upon encountering antigen in the tubules, resident DCs are only able to incite an initial T-cell response (IL2
production and T-cell clone formation), which merely primes the node for the possibility of dealing with
infection. A full-scale sustained immune response doesnt seem to occur until/unless antigen-presenting DCs
primed directly at the site of infection arrive in the node hours later and induce the activated resident DCs to
keep expressing the IL2 receptor and produce effector T-cells (Itano, et al., 2003). As antigen-presenting cells,
DCs are key players in the development of an immune response, effectively bridging the gap between innate
and acquired immunity. Only they can activate nave T cells (von der Weid & Rainey, 2010) which only reside
within lymph nodes & other SLO (Jenkins, et al., 2001). Dendritic cell apoptosis post antigen-presentation in
lymph nodes appears to be an essential immumoregulatory method for preventing hypervigilant
immunoreactivity (Hildeman, Jorgensen, & Kappler, 2007).

The intranodal tubular conduit system is also proposed to be a messenger system linking afferent lymph flow
messages of inflammation with recruitment of leukocytes from the bloodstream. The idea is that chemokine
messages of inflammation from areas of infection/injury flow via the lymph vessels to the downstream nodes
nearest it in the network. It is thought that these chemokines flow directly through the tubular system to the
HEV lumen where their messages can then pass into the systemic bloodstream circulation and recruit leukocytes
specific to the problem at hand to nodes local to the problematic area. Because lymph fluid flows directly
through the nodal tubular system to the HEV, the tiny diameter of this filtration system acts as a protective
mechanism, preventing PPMOs (viruses and bacteria, for instance) from entering the systemic blood circulation
(Roozendaal, et al., 2008).

These findings are all indicative of highly specialized functional regions and selective immunocyte trafficking
through lymph nodes, a stark contrast to the popular view of nodes as simply a storehouse for immunocytes. It
is at the lymph node level that the efficiency and appropriateness of the immune response is determined.
In many causes of injury, infection, and inflammation (See Table 2), lymph flow dynamics are influenced by
inflammatory mediators both at the site of damage and along lymphatic vessels. Both lymph flow and lymph
vessel proliferation increase, which helps to reduce edema and remove leucocytes, inflammatory mediators,
cytokines, and waste products from the interstitial fluid (von der Weid, 2001). Extracellular matrix remodeling
and lymphatic vessel morphological changes are associated with both mild and severe persistent allergic rhinitis
(Kim, et al., 2010). Proteoglycan deposition, collagen deposition, and number and length of lymphatic
endothelial vessels were all increased in allergic nasal tissue (Kim, et al., 2010). This subepithelial fibrotic
deposition of ECM components is believed to contribute to nasal obstruction. It is unclear whether the
lymphatic changes are contributors to the pathology or are instead working to remove obstruction and
extravasation of inflammatory oedema from the nasal interstitial fluid. What is certain is that reduced lymph
vessel presence in the lung epithelia of asthmatics has been associated with asthmatic fatality (Ebina, 2008).

Another key component of the ECM is the glycosaminoglycan hyaluronan (HA) (Foldi & Foldi, 2006). HAs many
functions in the lymphatic vasculature and nodes include influencing ECM stability, leukocyte extravasation and
other cell adherence effects, water retention, inflammation promotion and remediation, tumor metastasis, and
potentially, local paracrine signaling of immunocompromise (Jackson, 2009). An adhesion molecule receptor
(CD44) on HA is responsible for recruiting T-cells to sites of inflammation and for helping to resolve the

inflammatory response (Teder, et al., 2002). However, too much hyaluronan or too many HA breakdown
products in the ground substance can impair lymph clearance so that it is never removed via lymph vessel flow
to the lymph nodes (Foldi & Foldi, 2006) or liver for breakdown. This complication prevents resolution of
inflammation and leads to pathological changes such as fibrotic lung injury (Noble & Jiang, 2006).

Escin, a constituent of American ginseng (Panax quinquefolius) (Duke, 2012), and horse chestnut (Aesculus
hippocastanum) is a hyaluronidase inhibitor which helps prevent degradation of HA in the ECM (Braun & Cohen,
2007). Horse chestnut whole plant extract is used to promote and normalize vascular integrity, prevent or
reduce hyperpermeability-associated oedema, and increase lymph flow (Braun & Cohen, 2007). Procyanidins in
grape (Vitis vinifera) fruit are hyaluronidase inhibitors as well, and so may prove protective to ECM-lymph
functional dynamics (Duke, 2012). As this brief example illustrates, because lymphatic research is in its infancy,
and so few phytomedical studies have been done, many herbal medicines are likely affecting lymphatic function
unbeknownst to those involved in prescribing and taking them. Since HA has both pro- and anti-inflammatory
effects, herbs that effect HA may be viewed as immunomodulatory at the lymphatic level.

In tissues where antigenic presence is responsible for chronic inflammatory response, T & B cells, DCs,
macrophages, and plasma cells have been observed to organize themselves into functional units, complete with
endothelial cells which function like nodal HEVs. These tertiary lymphoid organs (TLO) are capable of producing
an immune response when local SLO are overwhelmed or dysfunctional. Fortunately many lymphatic system
cells (afferent lymph vessels, sinus areas of the nodes and tonsils, mucosa and submucosa of small and large
intestine and appendix, thus far) express a receptor called D6. This receptor attracts chemokines involved in the
inflammatory process. It is believed that lymphatic endothelial cell (LEC) D6 acts as a decoy and scavenger
receptor which sequesters leucocytes, targets them for destruction, and inhibits their progress to lymph nodes,
helping to shut-off of inflammatory processes (Ji, 2007) such as TLO formation. It is currently unknown whether
TLO aggregates express D6 receptors or any other form of shutoff mechanism. Indeed, they are most often
found in areas of chronic inflammation. As it seems TLO formation potentially participates in a self-sustaining,
inflammation-perpetuating feedback loop, it may be best to direct therapeutic interventions at promoting
primary and SLO function (Aloisi & Pujol-Borrell, 2006).
Interestingly, while two pharmaceutical drugs (glucocortocoid steroid Dexamethasone and acetylsalicylic acid)
impaired lymphatic regenerative healing after surgical wounding, a micronized, purified flavonoid fraction
known as Daflon (a combination of the flavanone diglycoside hesperidin, from citrus fruit, with diosmin, a
semisynthetic form of hesperidin) speeded up post-incisional wound healing and acted as a lymphagogue once

vessels had regenerated (Greco, et al., 2006). As Daflon has demonstrated lymphagogue activities in animal
studies in vivo, and flavanones are credited with antioxidant and anti-inflammatory properties, regulating
capillary permeability, and tonifying blood vessels (Garg, 2001), perhaps flavanones exert similar actions on the
vessels of the lymphatic system, which share the same embryologic origin and are known to be activated by
some of the same inflammatory mediators. In fact, it is difficult to separate the effects of inflammation on
blood versus lymphatic vasculature. Increased interstitial fluid leaked from blood capillaries can itself cause
lymph vessels to contract (von der Weid & Muthuchamy, 2010), and NO from lymphatic endothelia is known to
regulate lymph muscle tone, so that NO produced by inflammatory immunocytes is likely to affect lymph vessel
contractility (von der Weid & Muthuchamy, 2010).
Dan Shen (Salvia miltiorrhiza), which is traditionally considered a bit of a blood moving herb, seems from
modern research to move the nodes and vessels of the lymphatic system, as well. A traditional Chinese herbal
preparation including S. miltiorrhiza has been used to successfully mediate ascites (a lymphopathology
associated with abnormal changes in osmotic pressure and venous portal hypertension that is characterized by
abnormal accumulation of fluid in the abdomen) likely via effects on NO mediation (Wu, Li, & Mao, 2001). In
rats with severe acute pancreatitis and obstructive jaundice, inflammatory byproducts, such as NO, can inflict
pathological changes in lymph nodes. These changes were prevented by injections of Salvia miltiorrhiza extract
(Xiping, et al., 2009). Additionally, tanshinones isolated from S. miltiorrhiza extract affect inflammatory cytokine
profile. Tanshiones decreased macrophage IL-12 production and inhibited IFN- production in murine lymph
nodes challenged with antigen (Kang, Chung, Kim, Ryu, & Kim, 2000). IFN- is secreted by activated T cells and
has been implicated in autoimmune disease and other inflammatory pathologies. IL-12 is producted by
dendritic cells, macrophages, and B-lymphoblastoid cells in response to antigenic stimulation and helps nave T
cells decide whether to differentiate into Th1 or Th2 subtypes (Kang, et al., 2000; Silverthorn, 2009).

Once activated, most T-cells die within lymphoid tissues. Importantly, this is not the case under inflammatory
conditions where, instead, two functional classes of memory T cells continue to thrive, and can spread
throughout the body. The significance of this is that antigenic stimulation in the presence of inflammation
produces an increased number of specific T cells capable of producing effector lymphokines throughout the
body via the preservation of two classes of memory T cells which either initiate immediate effector
lymphokine production in nonlymphoid tissue or recirculate through the lymph network where they rapidly
aquire the effector capability if they encounter antigen (Jenkins, et al., 2001, p. 23). With the current onslaught
of inflammatory and autoimmune conditions of modern times, herbal immunomodulation at this level could be
very useful.

Table 2. Inflammatory conditions associated with lymphoid neogenesis
Condition Tissue affected
Rheumatoid arthritis diarthrodial joints
Hashimotos hypothyroiditis thyroid gland
Graves hyperthyroidism thyroid gland
Myasthenia gravis thymus
Sjorgrens syndrome salivary glands
Multiple sclerosis central nervous system
Cryptogenic fibrosing alveolitis lungs
Primary sclerosing cholangitis and primary biliary cirrhosis liver
Ulcerative colitis gut
Crohns disease gut
Atherosclerosis arteries
Chronic hepatitis c liver
Helicobacter pylori- or Campylobacter pylori- induced
Chronic Lyme disease joints
Ductal breast carcinoma breasts
Adapted from Aloisi & Pujol-Borrell, 2006
Mucosa associated lymphatic tissue (MALT) lines the bodys entry orifices and is an essential part of our immune
defense. MALT is subdivided into many classes, such as the gut associated lymphatic tissue (GALT), which
encompasses the tonsils, adenoids, mesenteric lymph nodes (MLN), and Peyers patches. Intestinal GALT is the
site of fat absorption. Long-chain fatty acids, importantly essential fatty acids (EFA), cannot be absorbed directly
via bloodstream capillaries and may only enter the body via the lymphatic system (von der Weid & Rainey,
2010). In the intestinal villi, chylomicrons are expelled from their assembly sites in lumen epithelial cells into the
interstitial space where lymph capillaries (called lacteals) in the lamina propria absorb them into local lymphatic
flow to form chyle (Foldi & Foldi, 2006). This chyle travels through the lymphatic vasculature, entering the
bloodstream via the left subclavian vein, quite near the heart (von der Weid & Rainey, 2010). Chyle is not
filtered by the liver on its way there. This bypass of hepatic first pass metabolism is one reason the intestinal
lymphatic route of absorption is of interest in drug delivery (Iosio, et al., 2011). Fat-soluble vitamins (A,D,E,K)
are also absorbed via the lacteals (Foldi & Foldi, 2006). Importantly, lipids are also absorbed from the ECM all
throughout the body via the lymphatic vasculature (von der Weid & Rainey, 2010). If not, they either
accumulate in adipocytes or are consumed by macrophages and can lead to cardiovascular disease (von der
Weid & Rainey, 2010; Lemole, 2001).
In situations of decreased lymphatic pumping, (ie. lack of diaphramagtic breathing, lack of exercise, infection,
post-surgical lymphatic impediments, inflammation, and depressive tendencies, perhaps) insufficient lymphatic

flow and lymph fluid leakage seem to promote fat accumulation when oedema induces accumulation of
inflammatory mediators, fibroblasts, adipocytes, and differentiation of preadipocytes into adipocytes (von der
Weid & Rainey, 2010). Dendritic cells seem to be a key factor here. DCs express PPAR receptors, and PPAR is
implicated in both adipose tissue development and inflammation (von der Weid & Rainey, 2010). DCs also
potentially act as intermediaries between diet and immunity by securing fatty acids from the ample supply of
perinodal adipose tissue (or from afferent lymph itself) and bringing them back to the node to provide energy
and immune function support (von der Weid & Rainey, 2010, p. 704). The fat surrounding lymph nodes contains
more omega 6 and omega 3 PUFA than other surrounding adipose tissue (von der Weid & Rainey, 2010). Fat-
derived arachidonic acid eicosanoid metabolites are produced by lymphatic vessel endothelia in response to
vessel contractions and act as inflammatory mediators which self-regulate vessel contractility (von der Weid &
Rainey, 2010). So, dietary intake of fats could play an important role in determining the level of inflammatory
upregulation at the lymph node level. Dietary inputs may also affect systemic reactivity through antibody-
mediated effects on the GALT.
The atopic conditions, which include atopic dermatitis/eczema (AD), allergic rhinitis (hay fever), and asthma
(Wahn, 2008) are marked by the inherited propensity to respond immunologically to common naturally
occurring allergens with the continual production of IgE antibodies (Parslow, Stites, Terr, & Imboden, 2001, p.
349), many of which are dietary antigens sampled by antibodies in the GALT. Elias, Hatano, and Williams
recently proposed an expanded model of the traditional view of AD, which assumed internal mechanisms (IgE,
mast cell dysregulation, Th1/Th2 imbalance, etc.) were the primary driving factor in AD manifestation. Their
model suggests instead that increased membrane permeability (resulting from combined genetic and external
factors) is the causative factor in the development and persistence of AD (2008). In IgE-mediated inflammation,
mast cell degranulation leads to the release of histamine which induces an immediate phase of inflammatory
response (Parslow, Stites, Terr, & Imboden, 2001). Mast cell granules also attract or synthesize inflammatory
mediators (TNF-, eosinophils, and neutrophils, PAF, IL-4, AA metabolites) which usher in the late phase of
inflammatory response which generates skin redness, hardening, warmth, sustained itching, and burning
(Parslow, et al., 2001).
IgE isnt the only antibody implicated in MALT immune function; immunoglobulin A (IgA) is also a factor.
Deficiency or low levels of IgA are associated with an increased prevalence of atopic disease (Cookson, 2004,
p. 984). At mucosal epithelial cell surfaces and in lymphatic tissues, IgA, particularly sIgA, is a major effector cell
(Roitt, Brostoff, & Male, 1993; Corthesy, 2009). sIgA is an antibody which can traverse mucosal membranes
and helps prevent entry of infectious microorganisms (Roitt, Brostoff, & Male, 1993, p. 3.9) particularly through
preventing bacteria from binding to the external surfaces of epithelial cells in mucosally associated lymphatic

tissue (MALT) (Corthesy, 2009). There are more antibody-producing plasma cells in the MALT than anywhere
else in the body (Kuby, 1994).
Immunoglobulin A (IgA) plays an essential role in the human bodys humoral immune defenses (Kazeeva &
Shevelev, 2007). Though it is a minority in blood serum (comprising 10-15%), IgA is the main immunoglobulin in
many exocrine secretions, including tears, breastmilk, saliva, and mucosa lining most tracts leading to the
outside world (Kuby, 1994). Because this immunoglobulin is present in exocrine secretions, it is one of our first
lines of defense against infection, acting locally in the gastrointestinal, respiratory, and genitourinary tracts
(Martini & Bartholomew, 2003; Widmaier, Hershel, & Strang, 2006), and playing many varied roles in immune
defense. It interacts with both PPMOs and the beneficial commensal microbiotic community within the
digestive tract (Cerutti, 2008), and one of its essential functions is disabling potentially pathogenic
microorganisms (PPMOs) before they are able to inflict intracellular damage. IgA antibodies can act as opsonins,
linking phagocyte to antigen (Widmaier, Hershel, & Strang, 2006, p. 721). Membrane IgA, found on the
surface of B cells, functions as a vital intermediary molecule in humoral immunity. Its location allows it to act as
both a receptor for antigen and then a signaling molecule which activates effector memory B cells upon
subsequent contact with a previously encountered antigen (Cerutti, 2008). IgA can also activate an indirect,
secondary pathway that activates complement (Sigal & Ron, 1993). This immunoglobulin, synthesized in the
GALT by plasma and B cells in both organized (Peyers patches) and nonorganized (lamina propria) lymphoid
structures, may assist the mucosal lining in disabling antigens (Sigal & Ron, 1993). Further assistance comes
from T cells so that IgA is often viewed as being a bridge between humoral and innate immunity.
T cells at the GALT likely influence IgA in two ways. First, they may be able to enhance B-cell IgA production and
lead to an association, at B cell surfaces, between CD4-antigen-presenting T helper cells (also called T4 cells) and
the Fc section present on the IgA (Sigal & Ron, 1993). CD4 cells are able to respond only to antigens presented
in association with class II MHC molecules. These activated CD4 cells may engage in either cytotoxic or
noncytotoxic activity. For example, cytoxic activity of CD4 cells has been demonstrated against Epstein-Barr
virus infected cells in humans (Sigal & Ron, 1993). There appear to be antiviral roles for IgA in the mucosa and
beyond. Roitt, Brostoff, and Male note that sIgA is particularly important in protecting against viruses which
lack a viraemic phase (1993, p. 15.11) meaning those viruses not released from their host cells into the
bloodstream (Edgar, 2006). It is also believed that sIgA present in the genital mucosa plays a role in resistance
to HIV infection by preventing HIV from contacting mucosal surfaces, adhering to epithelial cells or crossing the
epithelial cell barrier (Cerutti, 2008, p. 432).

Upon encountering a PPMO, DCs release retinoic acid, which induces IgA+ B cells to migrate out of Peyers
patches, through the lymphatic and blood circulation, and back to gut receptors in the lamina propria.
Importantly, on this journey, they transition to IgA-secreting plasma cells (Cerutti, 2008). Via this class-switching
response to localized PPMO presence, the lymph system helps create a prophylactic barrier to infection along
the entire lamina propria, not just the site of the initial PPMO engagement.(Macpherson, Geuking, & McCoy,
It is also possible for IgA class switching to occur based on TLR signals received from microbial colonies in the
gut, a possible means of controlling their overgrowth (Cerutti, 2008). Commensal bacteria are noticed by DCs
and sIgA cells in the intestinal lumen and attach to them there. Yet these bacteria are ultimately denied entry
into the circulation. Commensals attached to sIgA are denied access by the intestinal epithelial layers, while DC-
attached commensals are permitted a bit further, as far as the mesenteric lymph nodes before being stopped.
When this system is functioning properly, there is separation enough between the systemic and local immune
responses to intestinal microflora to prevent an autoimmune response (Macpherson, Geuking, & McCoy, 2005).
These commensal bacteria function as a communication link between B cells, epithelial cells, and other
members of the mucosal immune community such as DCs. As such, their presence and function help determine
IgA activity in the gut (Cerutti, 2008).
IBD pathologies are associated with lymphatic dysfunction in the gut. The degree of mucosal inflammation
appears to determine the extent to which lacteals are dilated in intestinal ileitis (von der Weid & Rainey, 2010).
Under inflammatory conditions such as those found in ileitis, Crohns, and other bowel pathologies,
inflammation causes impaired lymphatic drainage and dendritic cells become trapped in local areas of
inflammation. Together with B- & T-cells, they form lymphoid aggregates, known as tertiary lymphoid organs
(TLO), whose proliferating immunocytes and cytokines (though working to clear the damage ) effectively
maintain inflammation and pathological changes (von der Weid & Rainey, 2010; Aloisi & Pujol-Borrell, 2006). In
Crohns disease, lymphoid chemokines can also lure mature DCs away from their usual movement toward
lymphoid organs, enticing them instead to aggregate and form T-cell activating TLO at the site of inflammation
(Middel, Raddatz, Gunawan, Haller, & Radzun, 2006). This impaired lymphatic drainage also prevents metabolic
wastes and PPMOs from being removed from the area, furthering the promotion of inflammation and pathology
(von der Weid & Muthuchamy, 2010). It appears that in ulcerative colitis, marked by only superficial tissue
changes relative to Crohns disease, the preserved function of lymphatic vessels (which are located deeper in the
gut lining) serves as a protective mechanism against pathological spread beyond the level of the mucosa (von
der Weid & Rainey, 2010).

Given the prevalence of lymphatic tissue in the gut, it is not surprising that multiple herbal inputs mediate GALT-
associated pathological changes. Wogonin, a flavone in Scutellaria baicalensis reduces the pathological
expression of some forms of IBD. In mice fed wogonin, mesenteric lymph node antibody production was
altered. IgE production was lower and IgA production was higher in wogonin-treated mice, possibly conferring
increased mucosal barrier function, thereby decreasing allergic reactivity and inflammatory response. A
potential mechanism for this effect is wogonin-induced regulation of T-cell differentiation, decreasing Th2
cytokine expression while encouraging Th1 expression (Lim, 2004). GALT immunoreactivity is further affected
via the flavanoid baicalin in S.baicalensis which induces DC apoptosis, specifically, greater apoptotic induction of
immature DCs than of mature (Zhang, et al., 2011). S. baicalensis has activity in other areas which would
modify lymphatic function as well: it is implicated in cholesterol reduction, and is considered an anti-
inflammatory (via chemokine modulation, arachidonic acid modulating, and antioxidant pathways), anti-allergic,
and antimicrobial agent with vascular affinity. Baical skullcap also posseses some anxiolytic activity, important
in mediating stress-induced upregulation of immunity (Braun & Cohen, 2007). A ginsenoside-containing extract
has also been found to increase the number of IgA positive cells in a murine model (Biondo, Goruk, Ruth,
O'Connell, & Field, 2008). Since IgA antibodies (and other immunological pathways) become activated via
antigen-sampling DCs in the GALT (Cerutti, 2008), these effects on IgA expression demonstrate ways in which
herbal constituents can affect immunity via lymphatic pathways. The roles of IgA and DCs in MALT-driven
immunity described above provide other theoretical possibilities for the pharmacological actions of such IgA-
modifying herbs.
Aqueous extracts of the fungi Cordyceps sinensis appear to influence multiple facets of the lymphatic immune
system. It is considered an anti-tumor, immunomodulatory agent. A recent murine study revealed the ability of
C. sinensis to mediate allergic reactivity to food antigen via modification of antibody and cytokine production in
mesenteric lymph nodes (MLN). Mice fed this fungus demonstrated increased IgA and decreased IgE production
(Park, et al., 2008). As described above, IgE is one measure of allergic responsiveness and IgA is known to
mediate immune system involvement via MLN DC. C. sinensis treated mice also increased IFN- and IL-2 (Th1
cytokine) concentrations in MLN while decreasing IL-4 and IL-10 (Th2 cytokine) concentrations, potentially
indicating the ability of cordyceps to induce an allergy and inflammation-decreasing Th2-Th1 shift.
Herbal profile: Calendula officinalis
With its long history of both traditional and modern use, calendula (Calendula officinalis) may be the
quintessential lymphatic plant, as it encourages the bodys immunomodulatory, lymphatic cleansing, and wound
healing mechanisms. In his 19
century investigations of the herb, German homeopathic physician, Dr. Thorer,

(who administered topical herbal not homeopathic - preparations of calendula as a sort of sun tea infusion to
which he sometimes added alcohol) found its wound-healing effects to be unsurpassed, particularly as an anti-
suppurative, anti-scarring vulnerary. His work appears to have popularized calendula as the preferred treatment
for deep & surface lacerations (whereas arnica would have previously been used) (Hempel, 1848). Grieve
mentions its traditional immunomodulatory use in cases of ague (fever) from writings as early as the 1600s
(1971). Today, allopathic medicine might view this as potentially speaking to its ability to downregulate
inflammatory cytokine-driven febrile response. Given what we now know about the lymphatic vessels role in
draining inflammatory exudates from wound sites -- thus delivering waste products to nodes to be consumed
by macrophages and making room in the ECM for nutrients and granulation components to be delivered to
wound sites (Paupert, et al., 2011; Greco, et al., 2006) -- coupled with lymph nodes pivotal role in switching on
& off appropriate immune responses (Roozendaal, et al., 2008), its easy to see the value of calendula in
preventing suppuration and promoting healthy granulation in wound healing. Perhaps this anti-suppurative
action is related to the ability of calendula to inhibit lymphocyte proliferation (Amirghofran, Azadbakht, &
Karimi, 2000).
It has been noted that in wounded tissue, formation of fibrotic tissue and scarring induces lymph vessel
fibrosis/thickening prevents draining of fluids, and promotes further pathological changes (Paupert, et al., 2011).
We know that in normal wound repair, when lymphatic vessel function is reinstated as expected, lymph
transport returns and physiological functioning is restored (Foldi & Foldi, 2006). Perhaps the
prevention/reversal of ECM connective tissue damage and reinstatement of lymph vessel integrity and flow are
the explanatory mechanisms for calendulas historical prowess as a promoter of wound healing with almost no
While no studies have measured its particular effects on lymphatics, modern research has begun to sample the
immunomodulatory, vulnerary, antimicrobial, anti-inflammatory, and anti-oedema activity of calendula. Its
anti-inflammatory effects are attributed to the presence of the terpenoids faradiol, amidiol, and calenduladiol
(Braun & Cohen, 2007). Triterpenoid saponins found in calendula are believed to confer gastroprotective effects
through protection of GIT mucous membranes (Ebadi, 2002). At least part of its immunomodulatory effects
result from the herbs polysaccharide content (Ganora, 2009) which stimulates phagocytosis of granulocytes. It
is believed that this affect occurs through contact with immunoactive tissue, such as the GALT (Ganora, 2009).
As the lymphatic system strongly influences many of the aforementioned actions, further research will likely
cement calendulas place as a lymphatic herb in our modern materia medica. The golden sunshiny calendula
flower also has a long history of being used to promote joy (Grieve, 1971; Culpeper), which seems to be
additional good medicine for removing any negative emotions (melancholy) or stressors hanging on in the ECM.

Challenges of doing this research
Lymphology has only been recognized in allopathic medicine as a distinct discipline since 1966 (Dieter, et al.,
2011). Study has been impeded since lymphatic vessels collapse after death, making fluid dynamics
unobservable in cadaver studies. Until the very recent advent of imaging techniques such as various
lymphographies and radiotracer limphoscintigraphy, lymph flow has also been difficult to visualize in the living
system. Given these challenges, there is not yet a clear physiological understanding of the role of the lymph
system. Accordingly, most current research on lymphatics, and what little herbal research exists, has been
executed in in vitro or animal models, a great challenge in a system where dynamic movement is inherent in its
function. Regardless, lymphtic function remains an essential component of both maintenance of wellness and
resolution of disease. As lymph physiology becomes clearer, its my sincere hope that herbal research in this
area will become elucidated as well.


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