ORIGINAL ARTICLE

Comparison of levels of inflammatory

mediators IL-1␤ and ␤G in gingival crevicular
fluid from molars, premolars, and incisors
during rapid palatal expansion
Sappho Tzannetou,a Stella Efstratiadis,b Olivier Nicolay,c John Grbic,d and Ira Lamstere
New York, NY, and Athens, Greece

Introduction: Previously, we reported fluctuation of the levels of the inflammatory mediators interleukin-1␤
(⌱L-1␤) and ␤-glucuronidase (␤G) in gingival crevicular fluid (GCF) from the maxillary first molars in adolescents
undergoing rapid palatal expansion. In this study, we compared the responses of IL-1␤ and ␤G in the GCF of the
maxillary first molars, first premolars, and central incisors during palatal expansion at the same patients.
Methods: Nine patients requiring palatal expansion were selected at the postdoctoral orthodontic clinic at
Columbia University College of Dental Medicine. Each patient received periodontal prophylaxis and instructions
in proper home care including rinsing with chlorhexidine. Four weeks after periodontal prophylaxis, a modified
hyrax appliance was placed. The jackscrew was activated twice daily until the appropriate expansion was
achieved. GCF samples were collected before and after periodontal prophylaxis and during passive wearing of
the appliance, active orthodontic treatment, and retention. Fluid samples were collected with filter paper strips
and analyzed by ELISA and time-dependent fluorometry for IL-1␤ and ␤G, respectively. The values recorded after
periodontal prophylaxis were used as the baseline. Paired t tests were used to compare mediator levels at
baseline with the levels obtained at each subsequent observation. Results: The results validate that IL-1␤ and ␤G
are present in the GCF of adolescents, and, although their level decreases after a strict regimen of plaque control,
it increases during orthodontic or orthopedic movement. Moreover, this study demonstrates that both heavy and
light forces evoke increased levels of IL-1␤ and ␤G, stronger forces cause higher levels of inflammatory
mediators, and both IL-1␤ and ␤G respond to direct and indirect application of mechanical force to teeth.
Conclusions: This investigation corroborates previous findings that an inflammatory process occurs during
application of mechanical force to teeth. Although this inflammation is considered relatively aseptic, additional
inflammation, such as that induced by plaque accumulation, must be avoided during orthodontic or orthopedic
treatment. (Am J Orthod Dentofacial Orthop 2008;133:699-707)

T
here has been widespread use of palatal suture
opening to orthopedically expand a constricted
maxilla and to gain space for a crowded denti-
tion.1-6 However, we still lack knowledge about the
biochemical response of periodontal tissues involved in
this treatment.
a
Formerly postgraduate student and master degree candidate, Division of
Orthodontics, College of Dental Medicine, Columbia University, New York,
NY; currently private practice, Athens, Greece.
b
Professor, Division of Orthodontics, College of Dental Medicine, Columbia
University, New York, NY.
c
Associate professor, College of Dentistry, New York University, New York, NY.
d
Professor, Division of Periodontics and Oral Diagnosis, College of Dental
Medicine, Columbia University, New York, NY.
e
Professor and dean, College of Dental Medicine, Columbia University, New
York, NY.
Funded by American Association of Orthodontists Foundation Biomedical
Research Award to Dr. Stella Efstratiadis.
Reprint requests to: SapphoTzannetou, 9 Neapoleos St., Maroussi 151 23,
Greece; e-mail, sappho.tzannetou@gmx.net.
Submitted, July 2005; revised and accepted, March 2006.
0889-5406/$34.00
Copyright © 2008 by the American Association of Orthodontists.
doi:10.1016/j.ajodo.2006.03.044
It was suggested that during orthodontic treatment
biochemical mediators are released that trigger bone
remodeling, allowing tooth movement.7 Such media-
tors have been found in gingival crevicular fluid (GCF)
during orthodontic tooth movement.8-16
Interleukin-1␤ (IL-1␤), a proinflammatory cytokine
released from various cells, particularly macrophages,
fibroblasts, and osteoblasts, and the lysosomal enzyme
␤-glucuronidase (␤G), a marker of primary granule
release from polymorphonuclear leukocytes (PMN),
have been found in high levels in the GCF of teeth with
periodontal disease and have been associated with
periodontal destruction.17-21 Furthermore, some poly-
morphisms of the IL-1 gene cluster have been associ-
ated with advanced adult periodontitis,22 peri-implant
bone loss in heavy smokers,23 and increased levels of
IL-1␤ during orthodontic tooth movement.24 In con-
trast, the allele 1 of the IL-1␤ gene, associated with
decreased production of this cytokine in vivo, was
found to significantly increase the risk of external
699
700 Tzannetou et al
apical root resorption caused by orthodontic tooth
movement.25
The palatal expander, in addition to its orthopedic
effect on the suture, applies heavy forces on the anchor
teeth. Also, it results in a diastema between the maxil-
lary central incisors because of the sutural opening,
which is eliminated during retention by the application
of light forces produced by the elastic recoil of the
stretched supracrestal gingival fibers.26 Therefore, anal-
ysis of GCF allows the study of the biochemical
response of teeth and their supporting structures to both
heavy and light forces.
In our previous study, we examined the levels of the
inflammatory mediators from the maxillary first molars
subjected to orthopedic forces associated with rapid
palatal expansion.27 In this study, we compared the
responses of IL-1␤ and ␤G from the periodontal tissues
of maxillary first molars, first premolars, and central
incisors in adolescents undergoing rapid palatal expan-
sion.
MATERIAL AND METHODS
We described our methodology previously.27
Briefly, 9 adolescent patients (ages, 10-18 years; 5
boys, 4 girls) from the postdoctoral orthodontic clinic
of Columbia University College of Dental Medicine
were selected. All required opening of the palatal suture
as the first step in orthodontic treatment.
Periodontal prophylaxis and oral hygiene instruc-
tions were given to all patients before treatment. Each
patient was asked to use half an ounce of chlorhexidine
rinse twice daily (Peridex, Proctor and Gamble, Cin-
cinnati, Ohio) during the entire experimental period.
Ideal oral hygiene was important because our goal was
to investigate the changes in the levels of IL-1 ␤ and
␤G in GCF as a consequence of inflammation caused
by tooth movement rather than plaque accumulation.
A modified hyrax appliance was used.27 The first
molars were banded, and small bondable mesh pads
were bonded to the first premolars; all were connected
to the jackscrew. This design was used to promote oral
hygiene.
One week after placement, the jackscrew was acti-
vated once (0.25 mm) by the operator (S.T.) and once
by the patient or his or her guardian (total activation,
0.5 mm). The second activation occurred 24 hours later
by the patient (or guardian) in the orthodontist’s pres-
ence. Then the patient (or guardian) turned the jack-
screw once in the morning and once in the evening (0.5
mm every 24 hours) until the necessary expansion was
achieved.
To monitor the periodontal status of each patient
during the study, probing depth, gingival recession, and
American Journal of Orthodontics and Dentofacial Orthopedics
May 2008
dichotomous evaluations of plaque and bleeding on
probing at the mesiobuccal and mesiopalatal sites of the
maxillary first molars, first premolars, and central
incisors were recorded at the end of each observation.
Two to three weeks of active wear of this appliance
were generally required to achieve appropriate maxil-
lary expansion. The patients were observed according
to the following schedule.
Observation 1 (O1), control for observation 2 only.
Clinical data and GCF samples were collected from all
participants before treatment and oral-hygiene instruc-
tions. Then periodontal prophylaxis and oral hygiene
instructions and a bottle of chlorhexidine were given to
all subjects to be used daily.
Observation 2 (O2), control for all subsequent
observations, 14 days after O1. Clinical data and GCF
samples were collected.
Observation 3 (O3), 11 days after O2. Hyrax
appliance was placed, with no activation of the jack-
screw; clinical data and GCF samples were collected.
Observation 4 (O4), 7 days after O3. Clinical data
and GCF samples were collected; the jackscrew was
activated twice. At this visit, 7 days of passive appli-
ance wear were evaluated.
Observation 5 (O5), 24 hours after O4. Clinical data
and GCF samples were collected. At this visit, 24 hours
of active appliance wear were evaluated.
Observation 6 (O6), 6 days after O5. Clinical data
and GCF samples were collect. At this visit, 7 days of
active appliance wear were evaluated.
Observation 7 (O7), 7 days after O6. Clinical data
and GCF samples were collected. At this visit, 14 days
of active appliance wear were evaluated.
Observation 8 (O8), 7 days after O7. Only 5
patients needed a third week of activation. Clinical data
and GCF samples were collected. The appliance was
stabilized by locking the screw. At this visit, 21 days of
active appliance wear were evaluated.
Observation 9 (O9), 7 days after O8. Clinical data
and GCF samples were collected. At this visit, 7 days in
retention were evaluated.
Observation 10 (O10), 21 days after O9. Clinical
data and GCF samples were collected. At this visit, 28
days in retention were evaluated.
At each observation from O3 to O10, a set of
alginate impressions was taken and immediately
poured in stone to allow measurement of tooth move-
ment.
Maxillary occlusal radiographs were taken at O1
and O7 or O8 to verify the splitting of the palatal
suture.
GCF sampling took place in an area maintained at
21°C with 30% relative humidity.27 At each observa-
American Journal of Orthodontics and Dentofacial Orthopedics Tzannetou et al 701
Volume 133, Number 5

Fig 1. Mean percentages of plaque for molars, premolars, and incisors at the observation periods.
One-tailed paired t test was used. O1 was compared with O2 to evaluate the effect of periodontal
prophylaxis on plaque presence. O3 through O10 were compared with O2 to evaluate the effect of
orthodontic treatment on plaque (*P ⬍0.05, **P ⬍0.01, ***P ⬍0.001).

tion, GCF was collected for 30 seconds with methyl-
cellulose filter paper strips (Periopaper, Interstate Drug
Exchange, Amityville, NY) inserted in the gingival
crevice at the mesiobuccal and mesiopalatal aspects of
the first premolars and the central incisors. The fluid
volume from each strip was measured (Periotron,
model 6000, Interstate Drug Exchange).28 Immediately
after volume measurement, the filter strips from the
mesiobuccal sites were analyzed for ␤G activity. The
results were reported as total enzyme activity in units
per 30-second GCF sample.20
The GCF from the filter strips from the mesiopalatal
sites was then extracted by centrifugation. ELISA
(Multi-Kine ELISA kit, Cistron Biotechnology, Pine
Brook, NJ) was used to determine the levels of IL-1␤.
The results were reported as the total amount of IL-1␤
in picograms per 30-second GCF sample.
The relative stability of the palatal vault, recorded
with utility wax, was used to compare pretreatment and
posttreatment tooth movement. The distance between
the central incisors and the projection of the midpoint
between the buccal and lingual cusp tips of the first
premolars to the midpalatal reference line was mea-
sured with a Boley gauge to the nearest 0.1 mm.27
Statistical analysis
The mean values and standard errors at each obser-
vation period for total ␤G activity (units per 30-second
GCF sample), total IL-1␤ activity (picograms per
30-second GCF sample), plaque, bleeding on probing,
probing depth (mm), and gingival recession (mm) from
all subjects were calculated for the maxillary premolars
and the incisors. For the clinical parameters, the buccal
and palatal values were averaged.
A 1-tailed paired Student t test was used to deter-
mine whether there were any statistically significant
differences between the observation periods. Specifi-
cally, O1 was compared with O2 to determine the effect
of periodontal prophylaxis on the GCF levels of IL-1␤
and ␤G, and the clinical parameters. Then, O3 through
O10 were compared with O2, which was used as a
control to determine the effect of orthodontic or ortho-
pedic treatment on GCF levels of IL-1␤ and ␤G, and
the clinical parameters.
The mean amounts of tooth movement (in millime-
ters) between evaluations were also calculated.
RESULTS
Four patients needed 2 weeks of activation of the
appliance, and 5 needed 3 weeks of activation until the
appropriate expansion was achieved.
O3 and O4 described in our previous article were
included as 1 observation in this study.27
Clinical parameters
Plaque on the molars significantly decreased from
O1 to O2 (P ⬍0.01) and remained at a low level
throughout the trial (Fig 1). On the premolars, it
significantly decreased from O1 to O2 (P ⬍0.001),
remained low until O9, and increased at O10
(P ⬍0.01). Similarly, for the incisors, plaque accumu-
lation decreased from O1 to O2 (P ⬍0.01), remained
low until O9, and then increased at O10 (P ⬍0.05).
702 Tzannetou et al American Journal of Orthodontics and Dentofacial Orthopedics
May 2008

Fig 2. Mean percentages of bleeding on probing for molars, premolars, and incisors at the
observation periods. One-tailed paired t test was used. O1 was compared with O2 to evaluate the
effect of periodontal prophylaxis on bleeding on probing. O3 through O10 were compared with O2
to evaluate the effect of orthodontic treatment on bleeding on probing (*P ⬍0.05, **P ⬍0.01).

Fig 3. Mean percentages of probing depth for molars, premolars, and incisors at the observation
periods. One-tailed paired t test was used. O1 was compared with O2 to evaluate the effect of
periodontal prophylaxis on probing depth. O3 through O10 were compared with O2 to evaluate the
effect of orthodontic treatment on probing depth (*P ⬍0.05, **P ⬍0.01, ***P ⬍0.001).

For the molars, bleeding on probing was moderate,
and no statistically significant changes occurred
throughout the trial (Fig 2). For the premolars, bleeding
on probing significantly decreased from O1 to O2
(P ⬍0.01), remained moderate until O9, and increased
at O10 (P ⬍0.05). For the incisors, bleeding on probing
remained low throughout the study.
For the molars, mean probing depth significantly
increased at O3 (P ⬍0.05), O8 (P ⬍0.05), O9
(P ⬍0.05), and O10 (P ⬍0.001) (Fig 3). For the
premolars, probing depth significantly increased at O5
(P ⬍0.001) and remained elevated to O10. For the
incisors, probing depth significantly decreased at O2
(P ⬍0.01) and remained low during the study.
For the molars and premolars, gingival recession
was not observed. For the incisors, approximately 1
mm of recession was observed for most patients at the
palatal surface of the incisors 2 weeks after periodontal
prophylaxis; this was maintained during the trial.
Tooth movement
For the molars, a small amount of mean expansion
(0.08 ⫾ 0.22 mm) was observed at O6 (Fig 4). The
amounts of expansion were 0.63 ⫾ 0.15 mm at 24
American Journal of Orthodontics and Dentofacial Orthopedics
Volume 133, Number 5
Fig 4. Mean rates of tooth movement for molars, premolars, and incisors after placement of the
appliance (O5-O10).
hours, 1.28 ⫾ 0.17 mm at 1 week, 1.32 ⫾ 0.16 mm at
2 weeks, and 1.12 ⫾ 0.31 mm at 3 weeks of activation.
There were small relapses at 1 week (⫺0.11 ⫾ 0.21
mm) and 4 weeks (⫺0.12 ⫾ 0.21 mm) of retention.
For the premolars, a small amount of expansion
(0.18 ⫾ 01.10 mm) was observed at O4. The amounts
of expansion gradually increased during activation at
24 hours (0.56 ⫾ 0.07 mm), 1 week (0.94 ⫾ 0.14 mm),
and 2 weeks (1.32 ⫾ 0.16 mm). A smaller amount of
expansion was observed after 3 weeks of activation
(0.03 ⫾ 0.30 mm). Further expansion was observed at
1 week (0.50 ⫾ 0.17 mm) and 4 weeks (0.20 ⫾ 0.13
mm) after retention.
Diastemas between the central incisors began to
develop after 24 hours of appliance activation (0.22 ⫾
0.11 mm). The openings gradually increased after 1
week (0.93 ⫾ 0.30 mm) and 2 weeks (1.50 ⫾ 0.52 mm)
of activation. A smaller amount of expansion was
observed after 3 weeks of activation (0.82 ⫾ 0.37 mm).
After 1 week of retention, a negligible amount of
expansion was observed (0.02 ⫾ 0.44 mm). A relapse
(⫺1.16 ⫾ 0.37 mm) was observed after 4 weeks of
retention.
␤G levels in GCF
For the molars, the ␤G level significantly decreased
at O2 (control) (P ⬍0.05). Compared with O2, the ␤G
level significantly increased at O7 (P ⬍0.05), O8
(P ⬍0.01), O9 (P ⬍0.01), and O10 (P ⬍0.001) (Fig 5)
(Table I).
For the premolars, the ␤G level decreased but not
statistically significantly after periodontal prophylaxis,
oral hygiene instructions, and daily use of chlorhexi-
dine. However, compared with ␤G at O2, there were
Tzannetou et al 703
statistically significant increases in ␤G activity at O7
(P ⬍0.05), O8 (P ⬍0.05), and O10 (P ⬍0.05).
For the incisors, the ␤G level significantly de-
creased at O2 (control) (P ⬍0.01). Compared with O2,
␤G increased at O6 (P ⬍0.05), O7 (P ⬍0.05), and O10
(P ⬍0.01).
IL-1␤ levels in GCF
For the molars, the IL-1␤ level significantly de-
creased at O2 (control) (P ⬍0.01). Compared with O2,
the IL-1␤ level significantly increased at O5 (P ⬍0.01),
O6 (P ⬍0.001), O7 (P ⬍0.001), O8 (P ⬍0.01), O9
(P ⬍0.01), and O10 (P ⬍0.01) (Fig 6) (Table II).
For the premolars, the IL-1␤ level decreased but not
statistically significantly after periodontal prophylaxis,
oral hygiene instructions, and daily use of chlorhexi-
dine. However, compared with O2, there were statisti-
cally significant increases in IL-1␤ activity at O6
(P ⬍0.05), O7 (P ⬍0.05), O8 (P ⬍0.05), O9
(P ⬍0.01), and O10 (P ⬍0.01).
For the incisors, the IL-1␤ level significantly de-
creased at O2 (control) (P ⬍0.01). Compared with O2,
IL-1␤ significantly increased at O4 (P ⬍0.05), O6
(P ⬍0.05), O7 (P ⬍0.01), O9 (P ⬍0.05), and O10
(P ⬍0.01).
DISCUSSION
The findings from our previous study were that (1)
IL-1␤ and ␤G are present in the GCF of molars of
healthy adolescents, (2) the levels of these inflamma-
tory mediators decrease after a strict regimen of plaque
control, and (3) orthodontic or orthopedic forces ap-
plied to molars during rapid palatal expansion evoke
704 Tzannetou et al American Journal of Orthodontics and Dentofacial Orthopedics
May 2008

Fig 5. Mean values of ␤G level (units per 30-second GCF sample) for molars, premolars, and incisors
at the observation periods. One-tailed paired t test was used. O1 was compared with O2 to evaluate the
effect of periodontal prophylaxis on the ␤G level. O3 through O10 were compared with O2 to evaluate
the effect of orthodontic treatment on the ␤G level (*P ⬍0.05, **P ⬍0.01, ***P ⬍0.001).

Table I. ␤G mean values ⫾ standard error (units per 30-second GCF sample)
Molars Premolars Incisors

Mean SE Sig Mean SE Sig Mean SE Sig

O1 223.500 99.362 134.650 36.160 98.214 25.353

†
O2 67.167 21.038 * 76.567 17.704 NS 34.318 3.784
O3 44.342 8.492 NS 95.125 23.808 NS 56.511 15.591 NS
O4 40.067 11.565 NS 55.467 12.277 NS 37.600 9.151 NS
O5 78.119 18.508 NS 115.400 30.191 NS 49.294 9.951 NS
O6 82.950 21.105 NS 74.983 12.074 NS 57.000 11.888 *
O7 168.672 33.656 * 163.933 42.155 * 64.083 14.485 *
†
O8 210.640 47.628 123.020 33.695 * 76.180 17.376 NS
†
O9 155.044 32.653 122.417 33.753 NS 41.478 5.376 NS
‡ †
O10 233.428 36.912 121.767 19.228 * 67.117 9.991

NS, not significant; Sig, significance.

*P ⬍0.05; †P ⬍0.01; ‡P ⬍0.001.

changes in the levels of IL-1␤ and ␤G that can be
detected in GCF.27
The results of this study indicate that the levels of
IL-1␤ and ␤G collected in the GCF of maxillary
molars, first premolars, and central incisors of healthy
adolescents decrease after periodontal prophylaxis and
increase in response to application of orthodontic or
orthopedic force. More specifically, it seems that both
heavy (orthopedic) and light (from gingival fibers)
forces evoke biochemical activity and bone remodeling
during rapid palatal expansion; these are expressed by
increased levels of IL-1␤ and ␤G, as seen in this study.
A particularly interesting finding was that the 2 inflam-
matory mediators respond to both direct and indirect
mechanical stimulation to teeth.
Changes in plaque followed the same pattern for
molars, premolars, and incisors. Plaque decreased after
periodontal prophylaxis, remained low until O9, and
increased only at O10. This increase was probably due
to poor compliance by the patients at the end of the
trial. Therefore, the changes in the levels of ␤G and
IL-1␤ over time could not be attributed to plaque
accumulation.
Bleeding on probing for molars and premolars
remained moderate during the study; it was low for
incisors. Therefore, there was a better correlation of
plaque and tissue inflammation (measured by bleeding)
for the incisors than for the molars and the premolars.
However, the increases in bleeding on probing were not
statistically significant.
Gingival recession was not observed at the molars
and the premolars. For the incisors, approximately 1
mm of recession was observed for most patients. This
occurred on the palatal surface 2 weeks after periodon-
American Journal of Orthodontics and Dentofacial Orthopedics Tzannetou et al 705
Volume 133, Number 5

Fig 6. Mean values of IL-1␤ (picograms per 30-second GCF sample) for molars, premolars, and
incisors at the observation periods. One-tailed paired t test was used. O1 was compared with O2
to evaluate the effect of periodontal prophylaxis on the IL-1␤ level. O3 through O10 were compared
with O2 to evaluate the effect of orthodontic treatment on the IL-1␤ (*P ⬍0.05, **P ⬍0.01,
***P ⬍0.001).

Table II. IL-1␤ mean values ⫾ standard error (picograms per 30-second GCF sample)
Molars Premolars Incisors

Mean SE Sig Mean SE Sig Mean SE Sig

O1 1106.731 245.188 631.726 172.165 579.601 121.260

† †
O2 455.167 63.019 529.363 147.860 NS 279.957 68.572
O3 483.342 122.375 NS 516.219 165.856 NS 380.614 61.853 NS
O4 856.060 246.177 NS 1004.038 338.925 NS 773.355 150.365 *
†
O5 1050.444 231.376 530.223 98.022 NS 379.968 60.556 NS
‡
O6 1302.232 203.936 1072.379 161.607 * 589.872 115.113 *
‡ †
O7 1187.060 150.092 1045.687 172.951 * 1101.915 211.676
†
O8 1515.324 298.140 1404.169 320.010 * 894.330 274.076 NS
† †
O9 1375.245 241.227 965.684 133.366 939.200 235.705 *
† † †
O10 1831.541 521.698 1163.783 202.110 1016.960 210.478

NS, not significant; Sig, significance.

*P ⬍0.05; †P ⬍0.01; ‡P ⬍0.001.

tal prophylaxis and remained through the trial. The
recession was probably due to the reduction of inflam-
mation and was not true loss of attachment. This is
supported by the finding of low levels of ␤G at these
sites.20,21
There was incremental buccal movement at the
molars during passive placement of the appliance and
the activation period, and a small relapse during the
retention period. Interestingly, the premolars moved
from the time the appliance was placed until the end of
the experimental period. For the incisors, a diastema
was clinically observed 24 hours after appliance acti-
vation. The amount of opening gradually increased
during the activation period and after a week of
retention. Finally, a relapse took place at O10. Once the
suture is split, the incisors experience a light force,
tending to bring them toward the midline, that comes
from the stretched supracrestal gingival fibers.26 This
means that the final amount of tooth separation is the
net result of the 2 halves of the palate moving away
from each other minus the movement of the incisors
toward the midline (relapse). Molars and incisors fol-
lowed the expected pattern of movement during palatal
expansion, but premolars did not.26
While the levels of IL-1␤ and ␤G decreased in GCF
collected from molars, premolars, and incisors from
O1 to O2 (periodontal prophylaxis), these mediators
gradually increased from O2 to O10. The increase of
IL-1␤ preceded the increase of ␤G. Increased levels
of IL-1␤ indicated migration of phagocytotic cells that
706 Tzannetou et al
take part in the phagocytosis of necrotic tissue, the
degradation of hyalinized bone, and the repair process
during bone remodeling.29 If IL-1␤ in GCF is mainly
from macrophages, it appears that macrophage accu-
mulation precedes PMN leukocyte influx in the
aseptic inflammatory process associated with tooth
movement. This is opposite from what takes place in
bacteria-induced inflammation.30 In addition, since
IL-1␤ can be produced by virtually every nucleated cell
type including cells of epithelial tissues, increased
levels of this proinflammatory mediator could also be
the response of epithelial mucosal cells to early palatal
expansion.31
Increases in both IL-1␤ and ␤G levels were found
in earlier observation periods for molars compared with
premolars. This could be because the suture opens in a
V pattern, with the anterior area opening more than the
posterior due to zygomatic buttressing. Molars experi-
ence more dental than skeletal movement, and conse-
quently have earlier and more pronounced bone remod-
eling than premolars.
The increase in the levels of IL-1␤ and ␤G in
molars and premolars during the retention period could
be attributed to the orthodontic relapse and to the
tendency of the 2 maxillary segments to return to their
original position (orthopedic relapse). This would be
associated with remodeling of bone around the anchor
teeth.
Surprisingly, the central incisors responded simi-
larly to the molars and the premolars. Both IL-1␤ and
␤G levels significantly decreased immediately after the
strict regimen of oral hygiene (O1 to O2). The level of
IL-1␤ increased even 1 week after passive wearing of
the hyrax appliance. This could be attributed to the
force applied to the suture by placement of the rigid
appliance and the stretch of the palatal soft tissues. This
explanation is supported by the minute tipping of the
molars and the premolars at the same time. IL-1␤ might
trigger the production of interstitial collagenase from
fibroblasts or macrophages and the remodeling of the
connective tissue. The increase in the level of ␤G
occurred later than the increase in IL-1␤ (at O6). When
the diastema started closing, IL-1␤ was again observed
to first increase in GCF with ␤G at O10. IL-1␤ might
act as a chemotactic factor for PMN.32 This increase in
␤G activity could be the result of “scavenger” activity
by PMN, functioning to clear altered connective tissue
associated with periodontal remodeling that accompa-
nies tooth movement. Thus, it appears that even the
light force from the elastic recoil of the stretched
supracrestal gingival fibers evokes an inflammatory
process.
The levels of IL-1␤ and ␤G increased first at the
American Journal of Orthodontics and Dentofacial Orthopedics
May 2008
incisors, followed by the molars and the premolars.
This early sign of biochemical activity might be in
response to the stretched collagen fibers adjacent to the
suture; the force diffuses to the adjacent periodontal
tissues and GCF. Both heavy and light forces evoke
increased levels of IL-1␤ and ␤G, but the effect on the
molars, which experience the heaviest forces (resis-
tance to force), is more striking. Therefore, it seems
that the greater the force or, rather, the resistance to
force, the greater the inflammatory response. This
activity might also denote active tissue remodeling.
This study clearly demonstrates that, during orth-
odontic or orthopedic tooth movement, a relatively
aseptic inflammatory process occurs. Therefore, plaque
accumulation must be controlled during treatment to
prevent excessive inflammation. Extreme levels of
inflammation can be destructive to periodontal tissues
(loss of attachment, bone loss) and tooth structures
(root resorption).
Monitoring the levels of certain inflammatory me-
diators might be a clinically useful procedure. This is
noninvasive, easy, and relatively quick, and might help
to identify the degree of remodeling occurring in the
periodontal tissues during orthodontic or orthopedic
treatment. Furthermore, this information could guide
the clinician as to the appropriate time for orthodontic
or orthopedic retention.
The findings from this study and future studies
might help to establish the optimal levels of orthodontic
or orthopedic force, specifically forces that result in the
fastest tooth movement without pathologic conse-
quences such as root resorption or bone loss.
CONCLUSIONS
1. IL-1␤ and ␤G are present in the GCF of adoles-
cents, and their levels decrease after a strict regi-
men of plaque control and increase during orth-
odontic or orthopedic movement.
2. Both heavy and light forces evoke increased levels
of IL-1 ␤ and ␤G in GCF.
3. Higher forces cause higher levels of inflammatory
mediators.
4. Increases in IL-1␤ and ␤G occur as results of both
direct and indirect application of mechanical force
to teeth.
5. This investigation corroborates that an inflamma-
tory process takes place during application of me-
chanical force to teeth. Although this inflammation
is considered relatively aseptic, additional inflam-
mation, such as that induced by plaque accumula-
tion, must be avoided during orthodontic or ortho-
pedic treatment.
American Journal of Orthodontics and Dentofacial Orthopedics
Volume 133, Number 5
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