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Andreu, G.; Boccaccio, C.; Leguen, J. P.; Oleggini, M. (1992): Ultraviolet light-induced immunomodulation: a
possible new tool in organ transplantation. In: Annales de médecine interne, Jg. 143 Suppl 1, S. 52–56.
Schlagwörter Adjuvants, Immunologic; Animals; Bloodradiation effects; Humans;
Immunityradiation effects; Organ Transplantation; Ultraviolet Rays

Böhm, M.; Luger, T. A. (2004): [Alpha-melanocyte-stimulating hormone. Its current significance for dermatology].
In: Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete, Jg. 55, H. 5, S. 436–445.
Online verfügbar unter doi:10.1007/s00105-004-0729-0.
Abstract Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that was
originally characterized as a neuropeptide derived from the pituitary gland. alpha-
MSH is synthesized from pro-opiomelanocortin (POMC) by the action of specific
prohormone convertases which cleave POMC into alpha-MSH, adrenocorticotropin
and beta-endorphin. The various effects of alpha-MSH are mediated via
melanocortin receptors. The skin as well as the majority of cutaneous cell types
express POMC. Proinflammatory stimuli such as ultraviolet (UV) light induce POMC
expression and alpha-MSH secretion. Receptors for alpha-MSH are not only
expressed by melanocytes, where they mediate melanogenesis and proliferation,
but also by virtually every cutaneous cell type. Accordingly, alpha-MSH elicits a
plethora of biological actions in these cell types including immunomodulation,
protection from oxidative stress and UV-induced apoptosis, modulation of secretory
epithelial function and regulation of extracellular matrix composition. These actions
may be exploited in future by using super potent and truncated MSH peptides for
the treatment of various skin disorders including inflammatory dermatoses.
Schlagwörter Adjuvants, Immunologicmetabolism; Dermatologymethods; Humans;
Melanocytesmetabolism; Pro-Opiomelanocortinmetabolism;
Skinmetabolismradiation effects; Skin Diseasesdrug therapy; Ultraviolet Rays;
alpha-MSHmetabolismtherapeutic use

Byrne, Scott N.; Ahmed, Jarin; Halliday, Gary M.: Ultraviolet B but not A radiation activates suppressor B cells in
draining lymph nodes. In: Photochemistry and photobiology, Jg. 81, H. 6, S. 1366–1370. Online verfügbar unter
doi:10.1562/2005-04-20-RA-495.
Abstract Immunosuppressive doses of solar-simulated UV radiation activate lymph node B
cells that can suppress primary immunity by inhibiting the function of dendritic cells.
The aim of this study was to determine the waveband responsible for activation of
these suppressor B cells. We exposed C57BL/6 mice to various doses of either
UVA or UVB radiation and analyzed the number and activation state of lymph node
antigen-presenting cells (APC). Immunosuppressive doses of UVB but not UVA
activated B cells as assessed by major histocompatibility complex II (MHC II)
expression and doubled their numbers in draining lymph nodes. Higher doses of
UVA that were not immunosuppressive actually suppressed B cell activation. Our
results show that UVA and UVB suppress systemic immunity via different
mechanisms. Lymph node B cells are activated in response to immunosuppressive
doses of UVB but not UVA. Thus, the activation state of lymph node APC appears
to be important for UV immunomodulation.
Schlagwörter Animals; B-Lymphocytescytologyimmunologyradiation effects; Dendritic
Cellscytologyimmunologyradiation effects; Female; Immune Tolerance; Lymph
Nodesimmunology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Ultraviolet
Rays

Cooper, Kevin D.; Baron, Elma D.; Matsui, Mary S. (2003): Implications of UV-induced inflammation and
immunomodulation. In: Cutis; cutaneous medicine for the practitioner, Jg. 72, H. 3 Suppl, S. 11-5; discussion 16.
Abstract Sunscreens are the most effective and widely available interventions for sun
damage, other than sun avoidance or clothing. However, sun-screens vary widely in
their ability to screen various UV wavelength components. Testing methods for
sunscreens rely on UV-induced erythema to determine a sun protection factor
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(SPF), primarily a measure of UVB protection only. Determination of an immune
protection factor (IPF) has been proposed as an alternative or adjunctive measure
to SPF, and, indeed, recent studies show that the IPF can detect the added in vivo
functionality of sunscreens--such as high levels of UVA protection--that the SPF
cannot. Consensus on the definition of IPF, however, is required. Data are available
on quantification of the IPF for restoring the afferent or induction arm of contact
sensitivity, but other immune parameters also have been measured. A review of in
vivo studies in humans, in which sunscreens are used to intervene in UV-induced
modulation of immune response, cells, or cytokines, highlights the technical
variables and statistical approaches that must be standardized in the context of an
IPF for regulatory product claim purposes. Development of such IPF standards
would allow the integration of both UVB and non-UVB solar wave-band effect-
reversals. In addition, it could be applied to integrate the effects of other ingredients
with protective function (ie, antioxidants, retinoids, or other novel products) and spur
the development of more advanced and complete protection products.
Schlagwörter Humans; Inflammationetiologyimmunologypathology; Skinimmunologyradiation
effects; Sunscreening Agentspharmacology; Ultraviolet Raysadverse effects

Garssen, J.; van Loveren, H. (2001): Effects of ultraviolet exposure on the immune system. In: Critical reviews in
immunology, Jg. 21, H. 4, S. 359–397.
Abstract Depletion of stratospheric ozone and changes in lifestyle lead to an increased
exposure to ultraviolet (UV) wavebands, especially in the UVB region (280-320 nm).
Besides the beneficial effects of UV exposure, such as vitamin D production,
cosmetic tanning, and adaptation to solar UV, UV exposure can also have adverse
consequences on human health, notably sunburn, skin cancer, and ocular damage.
Over the last two and a half decades it has become evident that especially UVB
exposure and to a lesser extent UVA modulates specific as well as nonspecific
immune responses. Several reports have shown that this immunomodulation plays
at least a partial role in the induction of skin cancer. In addition, UVB exposure has
been demonstrated to impair resistance to some infections. On the other hand,
immunomodulation resulting from UVB exposure might be physiologically important
in inhibiting responses to neoantigens in the skin induced by UV exposure. In the
last 20 years UV has been used frequently as an experimental tool to unravel
immune responses-especially immune responses initiated in the skin (i.e.,
photoimmunology). In this review, the major mechanisms responsible for UV-
induced immunomodulation and its consequences are summarized.
Schlagwörter Animals; Cytokinesimmunology; Humans; Immune Systemradiation effects;
Photoreceptor Cellsimmunology; Ultraviolet Rays

Hart, P. H.; Grimbaldeston, M. A.; Finlay-Jones, J. J.: Sunlight, immunosuppression and skin cancer: role of
histamine and mast cells. In: Clinical and experimental pharmacology & physiology, Jg. 28, H. 1-2, S. 1–8.
Abstract 1. The development into tumours of skin cells transformed by ultraviolet (UV) B
radiation of wavelengths 290-320 nm is enhanced by the ability of UVB to suppress
an immune response that would otherwise destroy them. Ultraviolet B-induced
immunomodulation may be by multiple mechanisms, but generally manifests in an
antigen-presenting cell defect and an altered cytokine environment in the draining
lymph nodes. 2. Immune responses to microbial or self-antigens may be
dysfunctional by similar mechanisms following UVB exposure. 3. Earliest-acting
intermediates in the initiation of UVB-induced immunosuppression are the UVB
absorbers (photoreceptors) of the skin, notably DNA resulting in immunoregulatory
cytokine production, and trans-urocanic acid (UCA), which, upon isomerization to its
cis isomer, signals downstream immunosuppressive events. 4. In mice, dermal
mast cells are critical to UVB-induced systemic immunomodulation. In mice, there is
a functional link as well as a linear relationship between the prevalence of
histamine-staining dermal mast cells and the log of the dose of UVB required for
50% immunosuppression. Studies with histamine receptor antagonists support
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histamine as the main' product of mast cells involved. Histamine acts in large part
via a prostanoid-dependent pathway. 5. Approximately 50% of humans and greater
than 90% of patients with non-melanoma skin cancer are UVB susceptible for
suppression of a contact hypersensitivity response. Neither cytokine polymorphisms
nor UVB-induced levels of cis-UCA in irradiated skin have been linked to UVB
susceptibility. Patients with basal cell carcinomas (BCC) have an increased dermal
mast cell prevalence in non-sun-exposed buttock skin. We propose that mast cells
function in humans, as in mice, by initiating immunosuppression and, thereby,
allowing a permissive environment for BCC development.
Schlagwörter Animals; Carcinoma, Basal Cellimmunologymetabolism; Dermatitis,
Contactimmunologymetabolism; Histamineimmunologymetabolismradiation effects;
Humans; Immunosuppression; Mast Cellsimmunologymetabolismradiation effects;
Mice; Neoplasms, Radiation-Inducedimmunologymetabolism; Skin
Neoplasmsimmunologymetabolism; Ultraviolet Raysadverse effects

Hart, P. H.; Grimbaldeston, M. A.; Finlay-Jones, J. J.: Mast cells in UV-B-induced immunosuppression. In:
Journal of photochemistry and photobiology. B, Biology, Jg. 55, H. 2-3, S. 81–87.
Abstract Degranulating dermal mast cells in UV-B-irradiated skin have been implicated for
many years in the mechanisms of irradiation erythema. There is now considerable
evidence that dermal mast cells are important to the processes by which both UV-B
radiation and cis-urocanic acid (cis-UCA) suppress immune responses to
sensitizing antigens applied to non-irradiated/non-cis-UCA-exposed sites. Mast-cell-
depleted mice are resistant to the immunosuppressive effects of UV-B radiation and
cis-UCA for 'systemic' immunomodulation. However, these mice gain
responsiveness if the dorsal skin is reconstituted six weeks prior to irradiation or cis-
UCA administration at that site with cultured bone-marrow-derived mast cells from
+/+ mice. The molecular triggers for initiating mast-cell degranulation are being
actively sought. Evidence suggests that histamine, and not tumour necrosis factor
alpha, is the major mast-cell product that signals altered immune responses to
sensitizing antigens applied to non-irradiated, non-cis-UCA-exposed sites.
Histamine may have multiple roles, but experiments with indomethacin
administered to mice have shown that one process involves induction of prostanoid
production.
Schlagwörter Animals; Bone Marrow Cellscytology; Immunosuppression; Mast Cellsdrug
effectsimmunologyradiation effects; Mice; Skindrug effectsimmunologyradiation
effects; Ultraviolet Rays; Urocanic Acidpharmacology

Hurks, H. M.; van der Molen, R. G.; Out-Luiting, C.; Vermeer, B. J.; Claas, F. H.; Mommaas, A. M. (1997):
Differential effects of sunscreens on UVB-induced immunomodulation in humans. In: The Journal of
investigative dermatology, Jg. 109, H. 6, S. 699–703. Online verfügbar unter doi:10.1111/1523-
1747.ep12340652.
Abstract Ultraviolet radiation has been shown to suppress the (skin) immune system both in
animal species and in humans. Whether sunscreens can prevent
immunosuppression is a matter of debate. This study investigated the protective
capacity of a commercial sunscreen lotion in humans. Part of the right arm of
healthy volunteers was exposed to erythemagenic ultraviolet B doses of 160 mJ per
cm2 for four consecutive days. Before irradiation, sunscreen was applied either
directly onto the skin or onto a piece of quartz fixed to the skin (to avoid penetration
of the sunscreen in the epidermis where it cannot block the photoisomerization of
trans-urocanic acid in cis-urocanic acid in the stratum corneum). The control group
was irradiated without prior application of sunscreen. Four h after the last
irradiation, epidermal sheets were obtained by the suction-blister method from both
arms and epidermal cells were used as stimulator cells in the mixed epidermal cell
lymphocyte reaction. Responses directed to epidermal cells derived from irradiated
skin were expressed as percentages of responses directed to epidermal cells
derived from the nonirradiated left arm. The mixed epidermal cell lymphocyte
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reaction responses in the control group were found to be significantly increased
(205%). This enhancement of the mixed epidermal cell lymphocyte reaction
responses was associated with an influx of CD36+DR+ macrophages in the
irradiated skin. Application of the sunscreen, either onto a piece of quartz or directly
onto the skin, prevented the increase of the mixed epidermal cell lymphocyte
reaction responses and the influx of CD36+DR+ cells. In an earlier study,
volunteers were exposed three times weekly to suberythemagenic doses of
ultraviolet B over 4 wk, resulting in mixed epidermal cell lymphocyte reaction
responses that were decreased to 20%. The same sunscreen was not able to
prevent this suppression. These contradicting results indicate that the protective
effect of sunscreens with respect to ultraviolet-induced immunomodulation is
critically dependent on the choice of ultraviolet treatment.
Schlagwörter Humans; Lymphocytesdrug effectsradiation effects; Macrophagesdrug
effectsradiation effectsultrastructure; Skindrug effectsimmunologyradiation effects;
Sunscreening Agentspharmacology; Ultraviolet Raysadverse effects

(1988): Immunomodulation: UV radiation. In: Transplantation proceedings, Jg. 20, H. 1 Suppl 1, S. 302–308.
Schlagwörter Animals; Graft Enhancement, Immunologic; Graft Rejectionradiation effects; Graft
vs Host Diseaseprevention & control; Hematoporphyrinspharmacology;
Isoantigensimmunology; Lymphocyte Depletion; Mice; T-Lymphocytes,
Cytotoxicdrug effectsradiation effects; T-Lymphocytes, Regulatoryradiation effects;
Ultraviolet Rays

Luger, T. A.: Immunomodulation by UV light: role of neuropeptides. In: European journal of dermatology : EJD,
Jg. 8, H. 3, S. 198–199.
Schlagwörter Cells, Cultured; Humans; Immune Systemradiation effects;
Neuropeptidesphysiology; Pro-Opiomelanocortinphysiology; Skinradiation effects;
Ultraviolet Rays

Malina, L. (2003): [Urocanic acid and its role in the photoimmunomodulation process]. In: Casopís lékar̆ů
c̆eských, Jg. 142, H. 8, S. 470–473.
Abstract Urocanic acid (UCA) is a metabolite of the amino acid histidine. It represents an
important chromatophore in epidermis, which can absorb ultraviolet rays in UVB
and UVA region and sequentially convert it from trans- to cis-isomer. Cis-isomer is
not further degraded; it accumulates in the skin and is excreted with sweat and in
shedding keratin scales. UCA has several important functions, the regulation of the
homeostasis of the acidic cutaneous surface, the terminal differentiation of
epidermal cells and namely the immunomodulatory role. As and immunomodulator
UCA can suppress contact allergic reaction and the delayed hypersensitivity of the
organism. It can affect reactions mediated by Th-lymphocytes, cytokine system,
Langerhans cells, and by some neuropeptides. UCA is related to the development
of non-pigmented skin tumors (basaliomas) and indirectly also to pigmented tumors.
Cis-UCA can inhibit both the local and systemic resistance to infectious agents. In
the immunomodulation some adductive compounds with another important
cutaneous chromatophore DNA can participate.
Schlagwörter Adjuvants, Immunologic; Animals; Humans; Immune Tolerancedrug effectsradiation
effects; Skinimmunologyradiation effects; Ultraviolet Rays; Urocanic
Acidimmunologypharmacology

Norman, P. E.; Powell, J. T. (2005): Vitamin D, shedding light on the development of disease in peripheral
arteries. In: Arteriosclerosis, thrombosis, and vascular biology, Jg. 25, H. 1, S. 39–46. Online verfügbar unter
doi:10.1161/01.ATV.0000148450.56697.4a.
Abstract Vitamin D is generally associated with calcium metabolism, especially in the context
of uptake in the intestine and the formation and maintenance of bone. However,
vitamin D influences a wide range of metabolic systems through both genomic and
nongenomic pathways that have an impact on the properties of peripheral arteries.
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The genomic effects have wide importance for angiogenesis, elastogenesis, and
immunomodulation; the nongenomic effects have mainly been observed in the
presence of hypertension. Although some vitamin D is essential for cardiovascular
health, excess may have detrimental effects, particularly on elastogenesis and
inflammation of the arterial wall. Vitamin D is likely to have a role in the paradoxical
association between arterial calcification and osteoporosis. This review explores the
relationship between vitamin D and a range of physiological and pathological
processes relevant to peripheral arteries.
Schlagwörter Animals; Humans; Peripheral Vascular Diseasesepidemiology; Vitamin Dphysiology

Norval, M. (2001): Effects of solar radiation on the human immune system. In: Journal of photochemistry and
photobiology. B, Biology, Jg. 63, H. 1-3, S. 28–40.
Abstract On UV irradiation of the skin, a complex cascade of immunological changes results,
initiated by cutaneous chromophores and ending in suppression of some local and
systemic immune responses. In this review, the stages in this process are outlined
first, concentrating on the roles of DNA and urocanic acid as photoreceptors.
Evidence indicating UV-induced immunomodulation of delayed hypersensitivity and
resistance to infectious diseases in human subjects follows. Aspects of genetic
susceptibility to the immunosuppressive effects of UV exposure and extrapolation of
the data obtained in animal models to the human situation are included. Finally
uncertain and unknown factors relating to the impact of UV on the human immune
system are discussed.
Schlagwörter Animals; Communicable Diseases; Humans; Hypersensitivity, Delayedimmunology;
Immune Systemradiation effects; Immune Tolerance; Immunityradiation effects;
Solar Activity; Ultraviolet Raysadverse effects

Pamphilon, D. H.; Alnaqdy, A. A.; Wallington, T. B. (1991): Immunomodulation by ultraviolet light: clinical studies
and biological effects. In: Immunology today, Jg. 12, H. 4, S. 119–123.
Abstract The interest of immunologists in ultraviolet (UV) irradiation stems from observations
made in vitro and in vivo. In vitro, UV irradiation inhibits mitogen and mixed
lymphocyte culture (MLC) responses and in vivo, it can induce cutaneous anergy,
apparently via suppressor cells and serum factors. At present much interest is
focused on the possible use of UV irradiation to permit transfusion without
allosensitization and transplantation without either rejection or graft-versus-host
disease (GVHD). Here, Derwood Pamphilon and colleagues discuss the current
uses and potential of UV irradiation in transfusion and transplantation and relate
these to experimental evidence on its effects at the cellular level.
Schlagwörter Animals; Antigen-Presenting Cellsradiation effects; Antigens, Surfaceradiation
effects; Blood Plateletsimmunologyradiation effects; Blood Transfusion; Bone
Marrowimmunologyradiation effects; Bone Marrow Transplantationadverse effects;
Calciummetabolism; Cytokinessecretion; Dogs; Graft vs Host Diseaseprevention &
control; Humans; Immune Systemradiation effects; Immune Toleranceradiation
effects; Mice; Rats; Secretory Rateradiation effects; Transplantation
Immunologyradiation effects; Ultraviolet Rays

Roberts, J. E. (2000): Light and immunomodulation. In: Annals of the New York Academy of Sciences, Jg. 917,
S. 435–445.
Abstract The immune system is susceptible to a variety of stresses. Recent work in
neuroimmunology has begun to define how mood alteration, stress, the seasons,
and daily rhythms can have a profound effect on immune response through
hormonal modifications. Central to these factors may be light through an eye-brain
hormonal modulation. In adult primates, only visible light (400-700 nm) is received
by the retina. This photic energy is then transduced and delivered to the visual
cortex and, by an alternative pathway, to the suprachiasmatic nucleus (SCN), the
hypothalamic region that directs circadian rhythm. Visible light exposure also
modulates the pituitary and pineal glands, leading to neuroendocrine changes.
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Melatonin, norepinephrine, and acetylcholine decrease with light activation,
whereas cortisol, serotonin, GABA, and dopamine levels increase. The synthesis of
vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP), and
neuropeptide Y (NPY) in rat SCN has been shown to be modified by light. These
induced neuroendocrine changes can lead to alterations in mood and circadian
rhythm as well as immune modulation. An alternative pathway for immune
modulation by light is through the skin. Visible light (400-700 nm) can penetrate
epidermal and dermal layers of the skin and may directly interact with circulating
lymphocytes to modulate immune function. In contrast to visible light, in vivo
exposure to UV-B (280-320 nm) and UV-A (320-400 nm) radiation can alter normal
human immune function only by a skin-mediated response. It is therefore important,
when reporting neuroendocrine immune findings, to control the intensity, timing and
wavelength of ambient light.
Schlagwörter Adult; Humans; Immune Systemphysiology; Neuroimmunomodulation; Photic
Stimulation

Sandyk, R. (1993): Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis. In: The
International journal of neuroscience, Jg. 68, H. 3-4, S. 209–225.
Abstract Epidemiological studies demonstrate that the incidence of multiple sclerosis (MS) is
age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in
the mid 20s. It has been suggested that the manifestation of MS is dependent upon
having passed through the pubertal period. In the present communication, I propose
that critical changes in pineal melatonin secretion, which occur in temporal
relationship to the onset of puberty, are intimately related to the timing of onset of
the clinical manifestations of MS. Specifically, it is suggested that the fall in
melatonin secretion during the prepubertal period, which may disrupt pineal-
mediated immunomodulation, may stimulate either the reactivation of the infective
agent or increase the susceptibility to infection during the pubertal period. Similarly,
the rapid fall in melatonin secretion just prior to delivery may account for the
frequent occurrence of relapse in MS patients during the postpartum period. In
contrast, pregnancy, which is associated with high melatonin concentrations, is
often accompanied by remission of symptoms. Thus, the presence of high
melatonin levels may provide a protective effect, while a decline in melatonin
secretion may increase the risk for the development and exacerbation of the
disease. The melatonin hypothesis of MS may explain other epidemiological and
clinical phenomena associated with the disease such as the low incidence of MS in
the black African and American populations, the inverse correlation with sun light
and geomagnetic field exposure, the occurrence of relapses in relation to seasonal
changes and fluctuations in mood, and the association of MS with affective illness
and malignant disease. Therapeutically, this hypothesis implies that application of
bright light therapy or the use of other major synchronizers of circadian rhythms
such as sleep deprivation or application of external weak magnetic fields may be
beneficial in the treatment and/or prophylaxis of relapses in the disease.
Schlagwörter Adolescent; Adult; African Continental Ancestry Group; Age Factors; Age of Onset;
Endocrine System Diseasescomplicationsphysiopathology; Female; Humans;
Immune Complex Diseasesetiologyphysiopathology; Immune
Systemphysiopathology; Male; Melatoninsecretion; Middle Aged; Multiple
Sclerosisetiologyphysiopathologytherapy; Phototherapy; Pineal
Glandphysiopathology; Puberty

Sleijffers, Annemarie; Garssen, Johan; Vos, Joseph G.; Loveren, Henk (2004): Ultraviolet light and resistance to
infectious diseases. In: Journal of immunotoxicology, Jg. 1, H. 1, S. 3–14. Online verfügbar unter
doi:10.1080/15476910490438333.
Abstract Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune
responses in animals and humans. This immunomodulation can lead to positive
health effects especially with respect to certain autoimmune diseases and allergies.
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However, UV-induced immunomodulation has also been shown to be deleterious.
Experimental animal studies have revealed that UV exposure can impair the
resistance to many infectious agents, such as bacteria, parasites, viruses, and
fungi. Importantly, these effects are not restricted to skin-associated infections, but
also concern systemic infections. UV radiation induces a multistep process, locally
in the skin as well as systemically, that ultimately leads to immunosuppression. The
first event is the absorption of "UV" photons by chromophores, or so-called
photoreceptors, such as DNA and urocanic acid (UCA) in the upper cell layers of
the skin. Upon absorption of UV radiation, trans-UCA isomerizes to the cis-isomer.
Cis-UCA is likely the most important mediator of UV-induced immunosuppression,
as this compound has been shown to modulate the induction of contact type
hypersensitivity and delayed type hypersensitivity, allograft rejection, and the
functions of monocytes and T-lymphocytes as well as natural killer cells. The real
consequences of UV-induced immunomodulation on resistance to infectious
diseases for humans are not fully known. Risk estimations have been performed
through extrapolation of animal data, obtained from infection models, to the human
situation. This estimation indicated that UV doses relevant to outdoor exposure can
impair the human immune system sufficiently to have effects on resistance to
infections, but also indicated that human data are necessary to further quantify and
validate this risk estimation. Further information has been obtained from vaccination
studies in human volunteers as ethical reasons prohibit studies with infectious
agents. Studies in mice and human volunteers on the effects of prior UVB exposure
on hepatitis B vaccination responses revealed suppressed cellular and humoral
immune responses in mice but not in human volunteers. However, subgroups within
the performed human volunteer study made by determination of cytokine
polymorphisms or UVB-induced mediators, revealed that some individuals have
suppressed hepatitis B vaccination responses after UVB exposure. Thus, it might
be concluded that the human immune system can be affected by UVB exposure,
and decreased resistance to infectious diseases can be expected after sun
exposure.

Srinivasan, Venkataramanujan; Spence, D. Warren; Pandi-Perumal, Seithikurippu R.; Trakht, Ilya; Cardinali,
Daniel P. (2008): Therapeutic actions of melatonin in cancer: possible mechanisms. In: Integrative cancer
therapies, Jg. 7, H. 3, S. 189–203. Online verfügbar unter doi:10.1177/1534735408322846.
Abstract Melatonin is a phylogenetically well-preserved molecule with diverse physiological
functions. In addition to its well-known regulatory control of the sleep/wake cycle, as
well as circadian rhythms generally, melatonin is involved in immunomodulation,
hematopoiesis, and antioxidative processes. Recent human and animal studies
have now shown that melatonin also has important oncostatic properties. Both at
physiological and pharmacological doses melatonin exerts growth inhibitory effects
on breast cancer cell lines. In hepatomas, through its activation of MT1 and MT2
receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation
of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model
studies, melatonin has been shown to have preventative action against
nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth
of prostate tumors via activation of MT1 receptors thereby inducing translocation of
the androgen receptor to the cytoplasm and inhibition of the effect of endogenous
androgens. There is abundant evidence indicating that melatonin is involved in
preventing tumor initiation, promotion, and progression. The anticarcinogenic effect
of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and
apoptotic properties. Melatonin's oncostatic actions include the direct augmentation
of natural killer (NK) cell activity, which increases immunosurveillance, as well as
the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12,
and interferon (IFN)-gamma. In addition to its direct oncostatic action, melatonin
protects hematopoietic precursors from the toxic effect of anticancer
chemotherapeutic drugs. Melatonin secretion is impaired in patients suffering from
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breast cancer, endometrial cancer, or colorectal cancer. The increased incidence of
breast cancer and colorectal cancer seen in nurses and other night shift workers
suggests a possible link between diminished secretion of melatonin and increased
exposure to light during nighttime. The physiological surge of melatonin at night is
thus considered a "natural restraint" on tumor initiation, promotion, and progression.
Schlagwörter Animals; Antineoplastic Agentspharmacology; Cytokinesdrug effectsmetabolism;
Humans; Killer Cells, Naturaldrug effectsmetabolism;
Melatoninmetabolismpharmacology; Neoplasmsdrug therapyphysiopathology;
Receptor, Melatonin, MT1drug effectsmetabolism; Receptor, Melatonin, MT2drug
effectsmetabolism

Suke, Sanvidhan G.; Kumar, Achint; Ahmed, Rafat S.; Chakraborti, Ayanabha; Tripathi, A. K.; Mediratta, P. K.;
Banerjee, B. D. (2006): Protective effect of melatonin against propoxur-induced oxidative stress and
suppression of humoral immune response in rats. In: Indian journal of experimental biology, Jg. 44, H. 4, S.
312–315.
Abstract Effect of melatonin in attenuation of propoxur induced oxidative stress and
suppression of humoral immune response was studied in rats. Oral administration
of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days
treatment. Superoxide dismutase, catalase and glutathione were also altered
following propoxur exposure. In addition propoxur exposure markedly suppressed
humoral immune response as assessed by antibody titre and plaque forming cell
assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated
the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and
(c) immunotoxicity. Results have been discussed in the light of possible
immunopotentiating and antioxidant effects of melatonin to understand the influence
of oxidative stress on propoxur induced immunomodulation.
Schlagwörter Animals; Antibody Formationdrug effectsimmunology; Antioxidantsmetabolism;
Immunosuppressive Agentspharmacology; Male; Malondialdehydeblood;
Melatoninpharmacology; Oxidative Stressdrug effects; Propoxurantagonists &
inhibitorspharmacology; Rats; Rats, Wistar

Tran, T. Thanh-Nga; Schulman, Joshua; Fisher, David E. (2008): UV and pigmentation: molecular mechanisms
and social controversies. In: Pigment cell & melanoma research, Jg. 21, H. 5, S. 509–516. Online verfügbar
unter doi:10.1111/j.1755-148X.2008.00498.x.
Abstract Ultraviolet radiation (UVR) is an essential risk factor for the development of
premalignant skin lesions as well as of melanoma and non-melanoma skin cancer.
UVR exerts many effects on the skin, including tanning, carcinogenesis,
immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in
the maintenance of healthy bones as well as other purported beneficial effects,
amongst which is the potential for reducing risk of malignancy--though oral
supplementation is fully capable of maintaining systemic levels. The known medical
harm from UV exposure relates primarily to cancer of the skin--the most common
organ in man to be affected by cancer. In this review, we summarize the knowledge
about the ultraviolet (UV) response in regards to inflammation, immunosuppression,
carcinogenesis and the tanning response. We also discuss vit D and UV, as well as
public health implications of tanning behavior and commercial interests related to
the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR
exposure represents both a challenge and enormous opportunity in the realm of
skin cancer prevention.
Schlagwörter Humans; Immune Systemradiation effects; Lightadverse effects; Risk Factors;
Skinmetabolismpathologyradiation effects; Skin
Neoplasmsetiologypathologyphysiopathology; Skin
Pigmentationphysiologyradiation effects; Ultraviolet Raysadverse effects; Vitamin
Dmetabolism

Wintzen, M.; Yaar, M.; Burbach, J. P.; Gilchrest, B. A. (1996): Proopiomelanocortin gene product regulation in
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keratinocytes. In: The Journal of investigative dermatology, Jg. 106, H. 4, S. 673–678.
Abstract Proopiomelanocortin (POMC) is the precursor for adrenocorticotropic hormone,
melanocyte-stimulating hormones, beta-lipotropic hormone (beta LPH), and beta
endorphin. These peptides can function as neurotransmitters, modulate immune
responses, and affect melanogenesis. We investigated POMC expression and
protein processing in normal human keratinocytes. On Northern blot analysis, the
baseline expression of the 1.2-kb POMC transcript was upregulated by ultraviolet
radiation (UVR) or by stimulation with interleukin-1 alpha (IL-1 alpha) or phorbol 12-
tetradecanoate 13-acetate (TPA). On Western blot analysis, POMC, beta LPH, and
beta-endorphin were detected in cell extracts under baseline conditions. beta LPH
level increased substantially after UVR, IL-1 alpha, or TPA. Within 36 h after TPA
stimulation, beta-endorphin became undetectable in cell extracts, coinciding with an
increase of beta-endorphin-immunoreactive protein in the culture medium. Our data
establish that keratinocytes synthesize POMC protein as well as its derivatives beta
LPH and beta-endorphin, and that this process is modulated by TPA, IL-1A, and
UVR. beta LPH and beta-endorphin of keratinocyte origin may thus be involved in
melanogenesis and/or immunomodulation in the skin after sun exposure, and their
release into the circulation may also have systemic effects.
Schlagwörter Cells, Cultured; Gene Expression Regulation; Humans; Interleukin-1pharmacology;
Keratinocytesdrug effectsmetabolismradiation effects; Pro-
Opiomelanocortinanalysisgenetics; RNA, Messengeranalysis;
Tetradecanoylphorbol Acetatepharmacology; Ultraviolet Rays; beta-
Endorphinanalysis