CRANIOMAXILLOFACIAL TRAUMA

Increased Levels of Interleukin-6 in Synovial
Lavage Fluid From Patients With Mandibular
Condyle Fractures: Correlation With
Magnetic Resonance Evidence of Joint
Effusion
Shinnosuke Nogami, DDS,* Tetsu Takahashi, DDS, PhD,y Wataru Ariyoshi, DDS, PhD,zDaigo Yoshiga, DDS, PhD,x Yasuhiro Morimoto, DDS, PhD,kand Kensuke Yamauchi, DDS, PhD{
Purpose: The aim of the present study was to investigate the relation between magnetic resonance (MR)evidence of joint effusion and concentrations of proinflammatory cytokines, including interleukin (IL)-1b
and IL-6, in washed-out synovial fluid samples obtained from patients with mandibular condyle fractures.
Patients and Methods: Twenty-five joints in 23 patients with mandibular condyle fractures were
examined. Computed tomography was used to determine the position of the fracture and MR examination
was performed in all cases. Twenty-five joints underwent temporomandibular joint (TMJ) irrigation before
surgical treatment for the fractures. The detection rates and concentrations of the tested cytokines were
determined, and their relations to evidence of joint effusion and positions of the condylar fractures wereanalyzed.
Results: Six TMJ fractures were found in the head, 10 in the upper neck, 4 in the lower neck, and 5 in thesubcondyle. MR evidence of joint effusion was observed in 17 of 25 TMJs (68.0%). The detection rate andconcentration of IL-6 were significantly higher in patients with MR evidence of joint effusion and thosewith high condylar fractures. Moreover, there was a correlation between joint effusion grade and IL-6 concentration.
Conclusions:

The present findings showed a correlation between MR evidence of joint effusion and concentration of IL-6 in washed-out synovial fluid samples collected from patients with mandibular condylefractures. These results may provide support for arthrocentesis as a reasonable treatment modality forhigh condylar fractures.
Ó 2013 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 71:1050-1058, 2013

Maxillofacial

kProfessor and Chair, Division of Diagnostic Radiology, Department

Reconstructive Surgery, Department of Oral and Maxillofacialof Oral Diagnostic Science, Kyushu Dental College, Kitakyushu, Japan.

Surgery, Kyushu Dental College, Kitakyushu, Japan.
yProfessor and Chair, Division of Oral and Maxillofacial{Assistant Professor, Division of Oral and Maxillofacial
Reconstructive Surgery, Department of Oral Medicine and Surgery,

Reconstructive Surgery, Department of Oral and Maxillofacial

Tohoku University Graduate School of Dentistry, Sendai, Japan.

*AssistantProfessor,

Division

of

Oral

and

Surgery, Kyushu Dental College, Kitakyushu, Japan; Division of Oraland Maxillofacial Reconstructive Surgery, Department of Oral

Conflict of Interest Disclosures: None of the authors reported any
disclosures.

Medicine and Surgery, Tohoku University Graduate School of
Dentistry, Sendai, Japan.
zAssociate Professor, Division of Infections and Molecular Biology,
Department of Health Promotion, Kyushu Dental College, Kitakyushu,
Japan.
xAssistantProfessor,

Address correspondence and reprint request to Dr Nogami:
Department of Oral and Maxillofacial Surgery, Kyushu Dental

Division

of

Oral

and

Maxillofacial

Reconstructive Surgery, Department of Oral and Maxillofacial

College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka
803-8580, Japan; e-mail: r09nogami@fa.kyu-dent.ac.jp
Ó 2013 American Association of Oral and Maxillofacial Surgeons0278-2391/13/00106-7$36.00/0
http://dx.doi.org/10.1016/j.joms.2013.01.021

Surgery, Kyushu Dental College, Kitakyushu, Japan.

1050

1051

NOGAMI ET AL

Conservative treatment options for mandibular condyle fractures consist of intermaxillary fixation (IMF)
and rehabilitation, including jaw motion exercises,1,2
which have not changed since 1947.3 In contrast, aninternational consensus for the treatment of thosefractures has not been reached regarding the choiceof surgical reduction over nonsurgical modalities.4,5Even when a favorable outcome is achieved by conservative treatment with IMF, functional recovery requiresa lengthy and sometimes distressful rehabilitation. Fromexperimental findings, Ellis6 suggested that IMF delays
the recovery of the mandibular range of motion after orthognathic surgery. Thus, it is considered important toestablish a shorter and less painful treatment protocol
for patients with condylar fractures. Joint irrigation
with saline solution (arthrocentesis) has been usedtherapeutically for patients with pain and dysfunctionof the temporomandibular joint (TMJ),7 with outcomesof irrigation into the superior joint compartment foundto be satisfactory for various types of TMJ diseases.8-11
In addition, intra-articular corticosteroid injections
have been applied successfully as treatment for TMJ
pain and dysfunction,12 and Kondoh et al13 reported
that arthrocentesis for mandibular condyle fractures
was effective.
Mandibular condyle fractures frequently cause injury to soft tissues of the TMJ. Some studies haveused arthroscopy to show that intra-articular damage
generally occurs when the mandible is fractured.14,15
Furthermore, magnetic resonance (MR) evidence of
joint effusion, which is depicted on T2-weighted images as an increased signal in the joint compartment,
is frequently observed after a mandibular condylefracture.16 Although MR evidence of joint effusion
represents inflammatory changes, its clinical andbiological significance in the TMJ after such fracture
remains unclear. Segami et al17 reported that synovial
fluid from TMJs with internal derangement and osteoarthrosis with joint effusion contained higher concentrations of total proteins and the proinflammatory
cytokines interleukin (IL)-6 and IL-8 compared withsamples from TMJs without joint effusion.
The purpose of the present study was to investigate
the relations between MR evidence of joint effusionand concentrations of proinflammatory cytokines inwashed-out synovial fluid (SF) samples obtained frompatients with mandibular condyle fractures. Such MR
evidence was examined to determine the inflammatorychanges related to extravasation of protein molecules.
In addition, SF analyses of joint lavage (JL) fluid samples
collected from the superior joint space of the TMJ in patients with mandibular condyle fractures were performed, and the levels of inflammatory mediators,
including total protein and IL-1b and IL-6, were measured as a biological investigation of the effectivenessof arthrocentesis for a fractured TMJ with joint effusion.

Patients and Methods
PATIENTS AND CLINICAL ASSESSMENT

This prospective study was approved by the ethics
committee of Kyushu Dental College. The authors
examined 25 joints in 23 patients (16 male, 7 female;average age, 42.5 years; range, 19 to 80 years) withmandibular condyle fractures who underwent arthrocentesis for therapeutic purposes. In all cases, theTMJs were evaluated on MR images before treatment (Table 1).
Radiographic examinations included a panoramictranscranial view (open and closed mouth) and computed tomography to determine the position of themandibular fracture. Computed tomograms wereacquired using a Toshiba X Vision RE (Toshiba Co
Ltd, Tokyo, Japan). Helical scanning was performed
with a slice thickness of 1 to 2 mm and the following
parameters: 120 kVp, 220 ms, and table speed of
2 mm/second. The field of view was 18 cm (512 
512 matrix). The types of condylar fracture in relation
to the mandible were classified according to the classification of MacLennan,18 with some modifications.
Type I: fracture with no displacement
Type II: fracture deviation
Type III: fracture displacement with the condyle remaining in the fossa
Type IV: fracture deviation with dislocation
Type V: fracture displacement with dislocation
Three TMJs were classified as type I, 4 as type II, 5
as type III, 3 as type IV, and 10 as type V (Fig 1). The
positions of the fractures were divided into 4
areas—head, upper neck, lower neck, and subcondyle—with head fractures considered to occur at thejunction of the head and neck, essentially an intracapsular fracture. Fractures above the level of the depth of
the sigmoid notch and below the head were classified
as neck fractures and were divided further into the upper and lower neck areas. Those below the level of themost inferior point of the sigmoid notch were classified as subcondylar (Fig 2). The authors classified theposition of 6 TMJ fractures in the head, 10 in the upper
neck, 4 in the lower neck, and 5 in the subcondyle.
The types and condylar positions of the fractures arelisted in Table 1. The etiologies of the fractures werefalls in 14 patients (60.9%), assault in 6 (26.1%), sports
injury in 1 (4.3%), and traffic accidents in 2 (8.7%). In
addition, 7 patients had an additional mandibular body
fracture. The time from injury to the first visit ranged
from 0 to 21 days (average, 7 days), whereas thatfrom injury to MR examination ranged from 3 to 24
days (average, 11.3 days). In all patients, the MR examination was performed for diagnostic purposes before
beginning any treatment procedure, after obtaining

1052

INCREASED IL-6 IN MANDIBULAR CONDYLE FRACTURE

Table 1. CLINICAL DATA

Condylar Fracture
Patient
Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25

SF Analysis

Age (yr)

Side

GenderType

Position

Joint Effusion

IL-6 (pg/mL)

IL-1b (pg/mL)

64
35
31
23
19
24
71
25
40
27
52
63
62
19
19
80
26
47
21
58
72
72
23
40
55

L
L
L
L
L
L
R
L
L
L
L
R
R
L
R
R
L
L
L
R
R
L
R
L
L

F
M
M
M
M
F
F
M
F
M
M
M
M
F
F
F
M
F
M
M
M
M
F
M
M

V
V
III
V
I
I
III
I
V
V
IV
V
III
II
III
V
II
V
II
IV
V
V
II
IV
III

head
upper neckhead
upper necksubcondyleheadsubcondylesubcondyle
upper necklower neckupper neckhead
upper neckupper neckupper neckupper necklower necklower necksubcondyle
upper neck
head
head
subcondyle
upper necklower neck

B
B
B
B

104.1
16.1
44.3
180.9
ND
ND
ND
ND
13.3
ND
3.4
1,129.9
2.8
179.8
190.0
13.9
ND
178.1
ND
172.9
363.5
1,416.4
ND
0.3
ND

0.9
ND
ND
1.4
ND
10.2
ND
ND
ND
ND
7.1
0.6
ND
0.2
5.5
ND
0.96
ND
1.1
ND
16.9
5.3
2.5
ND
1.2

B
B
B
B
B
B
B
B
B
B
B
B
B

Abbreviations: F, female; IL, interleukin; L, left; M, male; ND, not determined; R, right; SF, synovial fluid.
Nogami et al. Increased IL-6 in Mandibular Condyle Fracture. J Oral Maxillofac Surg 2013.

informed consent, and using procedures approved by
the ethics committee of Kyushu Dental College. At thisinstitution, treatment for these fractures is dependent
on the position and type. In cases with fractures in theupper region of the condyle (n = 14), a closed reduction was performed, which included IMF for 5 days.
In cases with fractures in the lower region of the condyle or in those with a severely displaced condylar
fracture (n = 9), the authors used a retromandibular
approach or endoscopy-assisted open reduction andinternal fixation to perform an open reduction withdual mini-titanium plate fixation. In those 9 cases,
the SF sample was collected from the JL before performing the open reduction.
MR image examinations were performed in all cases
using a 1.5-T MR imaging scanner (Visert, Toshiba CoLtd) with a bilateral 3-inch dual-surface. Sagittal closedand open-mouth spin-echo T1-weighted images andsagittal and coronal closed-mouth fast spin-echo proton- and T2-weighted images were used for evaluation.
The parameters for the T1-weighted spin-echo sequence used were a repetition time of 1,050 ms, anecho time of 15 ms, a 160  288 matrix, a 15-cm fieldof view, and a slice thickness of 3 mm. Fast spin-echo

images used a repetition time of 3,500 ms and an
echo time of 108 ms for T2-weighted images. MR evidence of joint effusion was evaluated as previously described.19 Briefly, on T2-weighted images, joint
effusion was identified as an area of high signal intensity in the region of the superior or inferior joint space.
On proton- and T1-weighted images, the signal intensity in these areas was not increased. The joint was considered positive for joint effusion when more thana single line of high intensity was evident in at least 2
consecutive sagittal sections; otherwise, the joint wasconsidered negative. Evaluations of MR evidence of
joint effusion and the types and positions of mandibular condyle fractures were performed at least 2 times atdifferent time points by 2 of the authors (S.N. and T.T.)
who were blinded to the patients’ names and clinicalinformation. When there was disagreement, the final
assessment was reached by consensus. The degree of
joint effusion was determined as described by Segami
et al,20 and that in the superior compartment was divided into 4 grades: 0, no area of high signal intensity;
1, a line or spot of high intensity along the articularsurface; 2, a band of high intensity; and 3, collection
with pooling in the compartment.

1053

NOGAMI ET AL

FIGURE 1. Classification of mandibular condyle fracture types. Type I, fracture with no displacement; type II, fracture deviation; type III, fracture displacement; type IV, fracture deviation with dislocation; type V, fracture displacement with dislocation.
Nogami et al. Increased IL-6 in Mandibular Condyle Fracture. J Oral Maxillofac Surg 2013.

JL FLUID SAMPLE PREPARATIONAll SF samples were collected by the same author(T.T.), who is a TMJ specialist. SF samples of the JL obtained from the superior joint space were collectedfrom the patients and control subjects after a pumping
procedure by washing the joint with physiologic saline,

as previously described. Seven asymptomatic healthy
volunteers (5 male, 2 female; mean age, 35.2 years)
comprised the control group. They had no clinical signs
or symptoms involving the TMJ or disc derangement.
Briefly, after local anesthesia, 2 mL of physiologic saline solution was injected into the superior joint space,
and then the mouth was opened and closed to mix thesaline solution with the SF. The mixture of SF andsaline was then aspirated, and the procedure wasrepeated for a total of 10 times. Thereafter, the JL sample was collected, centrifuged at 800g for 5 minutes toremove cells, and stored at 80 C until being assayed.
The recovery of JL samples ranged from 60% to 120%,with a mean recovery of 100%. JL samples containing
blood resulting from active bleeding caused by the
sampling procedure were excluded from the study.
For all patients, informed consent was obtained before
treatment using a procedure approved by the ethics
committee of Kyushu Dental College.
MEASUREMENTS OF IL-1B AND IL-6

FIGURE 2. Classification of position of mandibular condyle fractures.
Nogami et al. Increased IL-6 in Mandibular Condyle Fracture.
J Oral Maxillofac Surg 2013.

Concentrations of the proinflammatory cytokines
IL-1b and IL-6 were determined using an enzymelinked immunosorbent assay kit (Quantikine; R&D
Systems, Inc, Minneapolis, MN) according to the manufacturer’s instructions. The detection limit for eachcytokine was 1 pg/mL. The same surgeon (S.N.) measured the concentrations of IL-1b and IL-6.

1054

INCREASED IL-6 IN MANDIBULAR CONDYLE FRACTURE

Table 2. POSITIONS OF MANDIBULAR CONDYLEFRACTURES AND JOINT EFFUSION

With JE

Without JE

5
10
2
0

1
0
2
5

Head (n = 6)Upper neck (n = 10)
Lower neck (n = 4)
Subcondyle (n = 5)
Abbreviation: JE, joint effusion.

Nogami et al. Increased IL-6 in Mandibular Condyle Fracture.
J Oral Maxillofac Surg 2013.

STATISTICAL ANALYSIS

Differences in concentrations of IL-1b and IL-6 wereanalyzed using the Mann-Whitney U test, with P < .05
considered statistically significant. The Spearman correlation coefficient was used to compare joint effusion
grade with the concentration of IL-1b and IL-6.

Results
MR evidence of joint effusion was observed in 17 of
25 TMJs (68.0% of all cases). That evidence was observed in all patients with high condylar fractures,
except for patient 6. Results of the enzyme-linked immunosorbent assay showed that IL-1b protein was detected in 13 TMJs (52.0%), whereas expression of IL-6
protein was observed in 16 TMJs (64.0%). In contrast,
neither IL-1b nor IL-6 was detected in any of the JL samples from the control group.
Furthermore, IL-6 was detected in all fractured TMJs
with joint effusion except for patient 10, whereas no
IL-6 expression was found in fractured TMJs without
joint effusion (Table 1). Detection of IL-1b was not as
typical as that of IL-6. MR evidence of joint effusion
was observed in nearly all patients with head andupper neck fractures (Table 2). The concentrationof IL-6 was significantly higher in TMJs with joint effusion compared with those without effusion (P < .05;
Fig 3A). However, there was no correlation between
concentration of IL-1b and the presence of joint
effusion (P > .05; Fig 3B). For the fracture position,high condylar fractures showed a significantly higher
concentration of IL-6 than low condylar fractures(P < .05; Fig 4). Moreover, there was a correlation between joint effusion grade and IL-6 concentration(P < .01; Fig 5A), whereas there was no correlation between joint effusion grade and IL-1b concentration(P > .05; Fig 5B).

Discussion
Because of the extended T2 period of free water,most body fluids are easily detected by T2-weighted
MR imaging, in which fluids have an intense signal com-

FIGURE 3. Concentrations of the cytokines A, interleukin-6 and B,
interleukin-1b in cases with and without joint effusion. Horizontal
bars indicate the mean value. ※P < .05, Mann-Whitney U test. C,
control group; IL, interleukin; JE (), no joint effusion; JE (+), withjoint effusion.
Nogami et al. Increased IL-6 in Mandibular Condyle Fracture.
J Oral Maxillofac Surg 2013.

pared with solid tissue.21,22 The vast majority oforthopedic studies of other joints, such as the knees
and hips, have shown that joint effusion is caused bytrauma, internal derangement, rheumatic disorders,hemophilia, and infections.23 Specifically, joint effusion
seems to be related to hemarthrosis and inflammatorychanges accompanying soft tissue injuries and arthralgia.23-26 In addition, some studies have noted that MR
evidence of joint effusion is frequently observed in
TMJs of patients with internal derangement andosteoarthritis (OA) of the TMJ.19,27,28 Although MR
evidence of joint effusion can be observed in jointcompartments of the TMJ after a condylar fracture,
little is known about its frequency and significance.
Sullivan et al29 reported evidence of joint effusion
by MR after condylar fractures, although they did not

NOGAMI ET AL

1055

FIGURE 4. Concentrations of interleukin-6 and mandibular condyle fracture positions. High condylar fractures, head and upperneck fractures; low condylar fractures, lower neck and subcondylar
fractures. ※P < .05, Mann-Whitney U test. IL, interleukin.
Nogami et al. Increased IL-6 in Mandibular Condyle Fracture.
J Oral Maxillofac Surg 2013.

investigate the frequency of effusion or its correlation
with fracture type and position. Schellhas30 also foundevidence of joint effusion by MR in patients with complicated acceleration-deceleration injuries. However,
because the time from injury to imaging differed significantly among cases (2 days to 24 months), it was notclear whether MR evidence of joint effusion was directly related to the soft tissue injuries or the subsequent clinical course. Because all the present patientswere referred to the authors’ department from otherhospitals, the periods from injury to imaging were significantly different.
Intra- and extracapsular condylar fractures are associated with hemoarthrosis.31 Using arthroscopy, Goss andBosanquest14 found intra-articular damage, including
hemarthrosis, and shedding of the disc and joint surfaces
in most examined TMJs. Jones and Van Sickels15 also reported the existence of hemarthrosis in 12 of 15 joints
by arthroscopy and found that the amount of blood
seen in the joint decreased as the delay from injury totreatment increased. These findings suggest that hemarthrosis is the major pathology occurring in the
TMJ after a condylar fracture. Because joint effusion isclosely related to hemarthrosis after joint injury,26 thepresent evidence of joint effusion in TMJs frequently
observed by MR imaging after condylar fractures probably represented hemarthrosis occurring in the joint.
Acute bleeding and hematomas are displayed as
high-intensity signals on T2-weighted images.21,32
Thus, MR evidence of joint effusion in the TMJ after
a mandibular condyle fracture may represent acutebleeding. However, this is unlikely for the following
reasons. Most hematomas present with bright signal
intensity and inhomogeneous signals on T1- andFIGURE 5. Distribution of grades of joint effusion and concentrations of A, interleukin-6 and B, interleukin-1b. Significant correlations are indicated by means values obtained in a Spearman
correlation coefficient by rank test. IL, interleukin.
Nogami et al. Increased IL-6 in Mandibular Condyle Fracture.
J Oral Maxillofac Surg 2013.

proton-weighted images.32 However, all the present
joints showed homogenous signals on T1- andproton-weighted images, and the signal intensity on
those images was not increased in any of the joints.
These findings suggest that MR evidence of joint effusion after a condylar fracture does not merely reflect
acute bleeding in the joint compartment.
In the present study, the mean time from injury to
MR imaging examination was 11.3 days (range, 3 to
24 days). Experimentally induced hemarthrosis resolves spontaneously within the first week after injury33; however, Goss and Bosanquest14 reported
that hemarthrosis spontaneously resolved within 5 to
7 days, with some residual hemosiderin visible insome joints for a longer period. Jones and Van Sickels15
also noted that the amount of blood in the joint decreased with an increased delay from injury to treatment, suggesting that hemarthrosis might subside

1056
within a relatively short period. Conversely, it is interesting to note that even at 10 days after injury evidence, joint effusion remained in 68.0% of the cases.
Thus, evidence of joint effusion on MR images after
a condylar fracture may be related to not only hemarthrosis but also joint inflammation, such as synovitis.
Previous studies have clearly shown that hemarthrosis leads to synovial hypertrophy and acute inflammation,33,34 and it has been shown that hyperemia andthickening persist. Inflammatory cells in synovial
tissue also persist for as long as 2 weeks after
injury.34 Therefore, MR evidence of joint effusionthat appears in joint compartments after a condylar
fracture also represents inflammatory changes andsubsequent extravasation of protein molecules because of increased permeability. The ultimate study
to clarify whether evidence of joint effusion after
a condylar fracture reflects the presence of hemarthrosis or joint inflammation, such as synovitis, would
include MR image examinations combined with arthroscopic evaluations of hemarthrosis and synovitis
in the same patients.
In the present study, all TMJs with dislocation examined after a condylar fracture showed MR evidence of
joint effusion, with joint effusion observed in the upper and lower joint compartments in 40% of the present patients. In addition, evidence of joint effusion
appeared more frequently in high compared withlow condylar fractures. Provided that MR evidence of
joint effusion is related to hemarthrosis or inflammatory changes occurring in the TMJ, these findings suggest that MR evidence of joint effusion after a condylar
fracture may reflect the severity of the impact on the
TMJ components. Interestingly, none of the TMJs incases with unilateral condylar fractures showed
evidence of effusion on the nonfractured side. In contrast, using arthroscopic findings, Goss and Bosanquest14 reported that TMJs showed greater damageon the nonfractured side compared with the fractured
side and explained that condylar neck fractures would
mechanically decrease the degree of direct intraarticular trauma by decompression. One possible explanation for not finding MR evidence of joint effusion
in contralateral TMJs is that mechanical damage tothe nonfractured side is not adequate to cause joint effusion. Interestingly, subcondylar fractures showed
lower levels of effusion in the present patients, which
may be explained by Goss and Bosanquest’s conceptthat mechanical stress is decompressed in such fractures, all of which were without dislocation, whereas
it is directly compressed in upper condylar fractures,
most of which also involved dislocation in the present
cohort.
Among the advantages of MR imaging as a diagnostic
modality are the lack of ionizing radiation and noninvasive characteristics.35 Although arthroscopy is a potent

INCREASED IL-6 IN MANDIBULAR CONDYLE FRACTURE

modality for investigating intra-articular damage after
condylar fractures, it is indicated only for patients
undergoing surgical treatment. Although preliminary,
the present study found that MR evidence of joint effusion in the TMJ may serve as a marker of severe intraarticular damage. Nevertheless, further studies withlarge numbers of joints and shorter periods until MR
image examination will be necessary to explore theclinical, biological, and biochemical significance ofMR evidence of joint effusion after mandibular condyle fractures.
Previous studies have found increased concentrations of IL-1b, tumor necrosis factor-a, and IL-6 in SF
from TMJs with degenerative changes.36-41 Those
cytokines may induce the release of proteinases,
stimulate the expression of matrix-degrading enzymes
and inflammatory mediators, and promote the degradation of cartilage and bone and inflammation in the
joint. IL-6 levels have been shown to be significantly increased in SF and serum obtained from patients withrheumatoid arthritis.42,43 Moreover, Kubota et al44
found that IL-6 was elevated in SF obtained from patients with TMJ and localized OA. Lee et al45 also reported higher concentrations of IL-6 in SF frompatients with temporomandibular disease comparedwith a healthy volunteer group.
In joints, this cytokine is produced by synovial cells,
monocytes, macrophages, and fibroblasts.41,44,46 IL-6also plays a major role in mediating inflammatory
and immune responses initiated by infection and injury. Previous reports have shown that IL-6 is a key
proinflammatory factor in arthritis, and studies ofanimal models have established that this cytokine
plays a main role in the pathogenesis of arthritis.47
IL-6 knockout mice are protected against adjuvantinduced polyarthritis, whereas the effects of IL-6 on
osteoclasts, osteoblasts, and bone remodeling arecomplex and vary among diseases.48
Donald et al49 reported experimental and clinical research on post-traumatic OA (PTOA). PTOA is closely
related to the energy delivered to the joint at thetime of injury and the resulting severity of articular surface damage.50,51 They also reported that P188 alone
or in combination with growth factors may have thepotential to prevent the development of PTOA. P188
affects stress-related p38 signaling, apoptosis-related
glycogen synthase kinase 3, and inflammation-related
IL-6 signaling.49,52 Lower levels of IL-6 may preventthe development of PTOA. Clinically, arthrocentesis
may have an effect on preventing the developmentof PTOA by decreasing the levels of IL-6 in the
joint cavity.
In the present study, IL-6 was detected only in casesof high condylar fractures with MR evidence of joint effusion. However, IL-1b was detected at the same rate as
IL-6 in the present patients. IL-1b appears earlier than

NOGAMI ET AL

IL-6. Because the time from injury to the collection of
SF samples was about 2 weeks in the present cases, theauthors presume that the concentration of IL-6 washigher than that of IL-1b in those samples. In addition,
the significant correlation between joint effusion
grade and concentration of IL-6 is an important finding. Thus, it is likely that IL-6 can be detected in casesof high condylar fractures with MR evidence of
joint effusion.
Segami et al20 reported that joint effusion wasclosely correlated with the severity of synovitis detected using an arthroscopic technique. Moreover,
Sandler et al41 noted that the presence of IL-6 wascorrelated with the degree of acute synovitis, whereas
IL-1b and tumor necrosis factor-a were not found insignificant levels within the superior joint space.
Decreased IL-6 levels in patients taking nonsteroidal
anti-inflammatory drugs have been shown in in vitro53
and in vivo54 experimental studies, which, as noted in
the latter study, may be related to the general antiinflammatory effect of the drugs or nonsteroidal antiinflammatory drugs exerting a direct effect on IL-6
production.
Kondoh et al13 found that intra-articular irrigationand corticosteroid injection resulted in quick recovery
of jaw function and shorter duration of distress in patients with unilateral fresh mandibular condyle fractures. The authors speculate that arthrocentesis may
cause lower levels of proinflammatory cytokines thatlead to synovitis.
In conclusion, the present results suggest that arthrocentesis may be a potent treatment modality forpatients with high condylar fractures, because it decreases the level of IL-6, which seems to be responsible for synovitis in the TMJ after a condylar fracture.
To obtain additional evidence, further studies regarding IL-6 concentrations and evaluations of synovitis
are currently being performed.

References
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2. Walker RV: Condylar fractures: Nonsurgical management. J Oral
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4. Banks P: A pragmatic approach to the management of condylar
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