The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study.

OBJECTIVES: We evaluated mRNA expression levels of genes that encode TGF-ß1; the TGF-ß1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated. METHODS: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy. Adhesive capsulitis was confirmed in all patients by magnetic resonance imaging. We also obtained specimens from 8 control patients who had underwent surgery for acute acromioclavicular joint dislocation and who had radiological indication of glenohumeral capsule alteration based on arthroscopic evaluation. mRNA expression in the synovium/capsule specimens was analyzed by quantitative reverse transcription PCR. The B2M and HPRT1 genes were used as references to normalize target gene expression in the shoulder tissue samples. RESULTS: The synovium/capsule samples from the patients with adhesive capsulitis had significantly higher TNC and FN1 expression than those from the controls. Additionally, symptom duration directly correlated with expression of TGFß1 receptor I. CONCLUSION: Elevated levels of TNC and FN1 expression may be a marker of capsule injury. Upregulation of TGFß1 receptor I seems to be dependent on symptom duration; therefore, TGFß signaling may be involved in adhesive capsulitis. As such, TNC, FN1 and TGFß1 receptor I may also play roles in adhesive capsulitis by contributing to capsule inflammation and fibrosis.

The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study

OBJECTIVES: We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated. METHODS: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy. Adhesive capsulitis was confirmed in all patients by magnetic resonance imaging. We also obtained specimens from 8 control patients who had underwent surgery for acute acromioclavicular joint dislocation and who had radiological indication of glenohumeral capsule alteration based on arthroscopic evaluation. mRNA expression in the synovium/capsule specimens was analyzed by quantitative reverse transcription PCR. The B2M and HPRT1 genes were used as references to normalize target gene expression in the shoulder tissue samples. RESULTS: The synovium/capsule samples from the patients with adhesive capsulitis had significantly higher TNC and FN1 expression than those from the controls. Additionally, symptom duration directly correlated with expression of TGFβ1 receptor I. CONCLUSION: Elevated levels of TNC and FN1 expression may be a marker of capsule injury. Upregulation of TGFβ1 receptor I seems to be dependent on symptom duration; therefore, TGFβ signaling may be involved in adhesive capsulitis. As such, TNC, FN1 and TGFβ1 receptor I may also play roles in adhesive capsulitis by contributing to capsule inflammation and fibrosis.

The pathogenesis of congenital radial head dislocation/subluxation.

The pathogenesis of congenital radial head dislocation/subluxation is unknown and has not been previously investigated. In this review, we explore the pathogenesis and define five different primary insults: collagen abnormalities, abnormal endochondral ossification of the developing growth plate, abnormalities of forearm ossification outside the growth plate, disproportionate growth of the radius and ulna, and altered HOX D expression/activity. Finally, the clinical relevance of our review is discussed.

Relationship between activity of gluthatione peroxidase and nitric oxide in synovial fluid and the progression of temporomandibular joint internal derangement.

The purposes of this study were to measure the activity of glutathione peroxidase (GPX) and nitric oxide (NO) in the synovial fluid of patients with temporomandibular joint (TMJ) internal derangement (ID) and to indicate the relationship between the activity of GPX and NO and the progress of the ID. Twenty-six patients with TMJ ID were identified and classified according to Wilkes staging through clinical and radiologic examinations. Levels of GPX were determined indirectly by a coupled reaction with glutathione reductase. Levels of NO were measured colorimetrically. The activity of GPX and NO was observed to be progressively increasing as the stage of the TMJ ID progressed. There were significant correlations between the 2 substances and the Wilkes stages. Oxidative stress may have a role in the pathogenesis of TMJ ID. In synovial fluid, GPX and NO activities are increased as the stage of the disease increased. Increase in the activities of GPX might not be enough to prevent progression of the TMJ ID.

[Experimental research on substance P content of hypothalamus and dorsal root ganglia in rats with lumbar vertebrae Gucuofeng model].

OBJECTIVE: To detect the effects of lumbar vertebrae Gucuofeng on the substance P content of hypothalamus and dorsal root ganglia in rat models. METHODS: A hundred and twenty SPF level SD male rats with the weight of 350 to 450 g were randomly divided into rotary fixation group (RF group), simple fixation group (SF group) and sham-operation group (Sham group). The external link fixation system was implanted into the L4-L6 of rats in RF group and SF group; and in RF group, that the L5 spinous process was rotated to the right resulted in L4, L5, L6 spinous process not collinear; in SF group, the external link fixation system was simply implanted and not rotated. The rats of Sham group were not implanted the external link fixation system and only open and suture. The substance P content of hypothalamus and dorsal root ganglia were detected at 1, 4, 8, 12 weeks after operation. RESULTS: Substance P content of hypothalamus in RF group and SF group was lower than Sham group at 1, 4, 8 weeks after operation (P<0.05). Substance P content of dorsal root ganglia was higher than Sham group at 1, 4, 8, 12 weeks after operation (P<0.05). There was no significant differences in the substance P content of hypothalamus among three groups at 12 weeks after operation (P>0.05). CONCLUSION: Lumbar vertebrae Gucuofeng can inhibit the analgesic activity of substance P in hypothalamus and promote the synthesis and transmission of substance P in dorsal root ganglia, so as to cause or aggravate the pain.

Antioxidant capacity of synovial fluid in the temporomandibular joint correlated with radiological morphology of temporomandibular disorders.

We investigated the correlation between the antioxidant capacity of synovial fluid and radiological findings of intra-articular structures in patients with disorders of the temporomandibular joint (TMJ). We recruited 21 patients (9 men and 12 women, aged 18-84 years of age) with such disorders, excluding myofascial pain and dysfunction syndrome, or other muscular disorders. The clinical variables recorded included age, sex, interincisal distance, and visual analogue pain scores (VAS). Radiological findings were obtained from diagnostic arthrogram and cone-beam computed tomography (CT). The antioxidant capacity of the synovial fluid was measured by chemiluminescence. Eleven patients were radiologically diagnosed with closed lock, and the remaining 10 with no closed lock. An anchored intra-articular disc was most often seen on cone-beam CT (n=19) followed by perforated disc (n=7), osteoarthrosis (n=7), and anterior disc displacement without reduction (n=5). Although there were no significant differences between antioxidant capacity and age, sex, VAS, or any findings on cone-beam CT, antioxidant capacity was significantly decreased in the patients with closed lock compared with those who did not have closed lock (p=0.02). The results suggest an association between the oxidative stress of the synovial fluid and closed-lock in disorders of the TMJ.

Investigation of an autologous blood treatment strategy for temporomandibular joint hypermobility in a pig model.

Many different surgical and non-surgical techniques are used for the treatment of temporomandibular joint (TMJ) hypermobility. One of these methods is autologous blood injection into the TMJ. The fate of the autologous blood used for treatment of recurring condylar dislocation is still not completely understood. The authors used 12 pigs (Sus scrota f. domestica) as a model species for autologous blood delivery into the TMJ. Blood injection was followed by histopathological analysis at different times after treatment (1h, 1, 2 and 4 weeks). Samples were examined by magnetic resonance imaging, macroscopic and histological methods. The deposition of the remaining blood was observed in the form of clots in the distal parts of the upper joint cavity 1h and 1 week after treatment. 2 weeks after treatment, small blood clots were still apparent in the distal part of the upper joint cavity. 4 weeks after surgery, no remnants of blood, changes or adhesions were apparent inside the TMJ. No morphological or histological changes were observed in the TMJ after the injection of autologous blood suggesting another mechanism is involved in the hypermobility treatment.

Expression of VEGF-receptors in TMJ synovium of rabbits with experimentally induced internal derangement.

Our aim was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in the synovium of the temporomandibular joints (TMJ) of rabbits with experimentally induced internal derangement. Internal derangement was experimentally induced in 52 rabbit TMJ, and established on the right side of TMJ while the left side was used as the control. Each joint and its control was evaluated by magnetic resonance imaging (MRI) and endoscopy. The synovial tissues on both sides were harvested after one, two, three, and four weeks. The expression of VEGFRs mRNA was investigated in the experimental joint and its control using real-time polymerase chain reaction (PCR). Internal derangement was successfully confirmed in 45 of the 52 of the experimental joints (87%) on the right side by MRI and endoscopy. In the first and fourth week, the VEGFR-2 mRNA expression was higher in the experimental joints than in the controls (P=0.008 and P=0.02). Meanwhile, the VEGFR-1 mRNA expression was up-regulated in the experimental group compared with the controls during the fourth week (P=0.02). However, we found no significant differences in VEGFR-3 mRNA expression in the two groups during the first and fourth weeks. During the second and third weeks, the mRNA expression of the three receptors did not differ significantly among the groups. Our data have shown increased expression of VEGFR-1 and VEGFR-2 mRNA in the synovium of rabbit TMJ with internal derangement, which indicates that VEGFR-1 and VEGFR-2 may have important roles in the processes of internal derangement and formation of adhesions.

Analysis of the cytokine profiles of the synovial fluid in a normal temporomandibular joint: preliminary study.

The purpose of this study was to compare the cytokine profiles of the synovial fluid from the temporomandibular joint (TMJ) spaces of normal individuals and temporomandibular disorder (TMD) patients. Thirty-four patients with planned orthognathic surgery did not present abnormalities of the TMJ on magnetic resonance images and radiographs and did not show the symptoms identified by the Research Diagnostic Criteria for TMD (RDC-TMD); as a result, they were assigned to the control group. Twenty-two patients who sought treatment for TMD during the same period were assigned to the TMD group. Synovial fluid was collected from superior TMJ spaces, and cytokine expression was analysed by an enzyme-linked immunosorbent assay (ELISA). Significant differences were tested using Fisher's exact test (p<0.05). Granulocyte Macrophage Colony stimulating Factor (GM-CSF), interferon (INF), interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α were detected in the TMD group, whereas no cytokines were detected in the control group. The most prevalent cytokines in the TMD group were IL-1ß, IL-6 and GM-CSF. IL-4 and IL-5 were not detected in either the TMD group or in the control group. None of the cytokines that were detected in patients with TMD were found in the articular spaces of normal individuals.

Potential biomarkers of temporomandibular joint disorders.

PURPOSE: The purpose of this study was to identify protein markers present in subjects with temporomandibular joint disorders (TMDs) and clicking compared with the levels in controls. MATERIALS AND METHODS: This was a pilot case-control study, and we report the preliminary results. Samples of joint aspirate collected from patients with TMDs and controls who had undergone surgery for a problem other than TMDs were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) and biotin-labeled-based protein arrays. The data obtained from these techniques were used to identify the proteins of interest, which were then quantitated using enzyme-linked immunosorbent assay (ELISA). The patient samples studied included joint aspirate collected clinically from the controls and patients and included samples from both the right and the left sides of each patient with a TMD. RESULTS: The 8 TMJ aspirate samples from 6 subjects included 5 aspirate samples from 4 patients and 3 from 2 controls. The greatest standardized protein concentration of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 (EG-VEGF/PK1) and D6 was found in both joints of the controls compared with the levels from the joints of the patients. With 1 exception, the standardized protein concentration was significantly lower in the patients than in the controls. The lower levels of EG-VEGF/PK1 and D6 in the patients compared with the controls suggest that these cytokines might be possible biomarkers for TMDs. CONCLUSION: In the present pilot study, greater levels of EG-VEGF/PK1 and D6 were found in the controls than in the patients with TMDs. Proteomic analysis of the proteins present in the diseased joints compared with those in the controls might help to identify proteins present when pain or degeneration of the joint occurs. The proteomic information might be useful in the development of future therapies.

Phenotypic features of carbohydrate sulfotransferase 3 (CHST3) deficiency in 24 patients: congenital dislocations and vertebral changes as principal diagnostic features.

We recently reported on the deficiency of carbohydrate sulfotransferase 3 (CHST3; chondroitin-6-sulfotransferase) in six subjects diagnosed with recessive Larsen syndrome or humero-spinal dysostosis [Hermanns et al. (2008); Am J Hum Genet 82:1368-1374]. Since then, we have identified 17 additional families with CHST3 mutations and we report here on a series of 24 patients in 23 families. The diagnostic hypothesis prior to molecular analysis had been: Larsen syndrome (15 families), humero-spinal dysostosis (four cases), chondrodysplasia with multiple dislocations (CDMD "Megarbane type"; two cases), Desbuquois syndrome (one case), and spondylo-epiphyseal dysplasia (one case). In spite of the different diagnostic labels, the clinical features in these patients were similar and included dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The most useful radiographic clues were the changes of the lumbar vertebrae. Twenty-four different CHST3 mutations were identified; 16 patients had homozygous mutations. We conclude that CHST3 deficiency presents at birth with congenital dislocations of knees, hips, and elbows, and is often diagnosed initially as Larsen syndrome, humero-spinal dysostosis, or chondrodysplasia with dislocations. The incidence of CHST3 deficiency seems to be higher than assumed so far. The clinical and radiographic pattern (joint dislocations, vertebral changes, normal carpal age, lack of facial flattening, and recessive inheritance) is characteristic and distinguishes CHST3 deficiency from other disorders with congenital dislocations such as filamin B-associated dominant Larsen syndrome and Desbuquois syndrome.

Occurrence and regional distribution of TRAIL and DR5 on temporomandibular joint discs: comparison of disc derangement with and without reduction.

BACKGROUND: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an apoptosis-inducing member of the TNF gene family which triggers apoptotic signals by interaction with its receptors. It has been suggested to be a major contributing factor to tissue degeneration. OBJECTIVE: The present study investigated, through immunohistochemistry, the regional expression of TRAIL and in temporomandibular joint (TMJ) disc of anterior disc displacement with reduction (ADDwR) and without reduction (ADDwoR) patients, to help determine the relationship between TMJ disc displacement and apoptosis. STUDY DESIGN: We studied 18 TMJ diseased discs affected by disc displacement without or with reduction and 4 normal TMJ discs. Specimens were processed for immunohistochemistry to evaluate TRAIL and its receptor DR5 expression. RESULTS: Disc tissues from internal derangements (both ADDwR and ADDwoR) exhibited a much higher percentage of TRAIL- and DR5-positive cells as well as stain intensity compared with normal tissue though with regional variation according to the portion of the disc. There was a significantly higher percentage of stained cells in the posterior disc attachment compared with the anterior or intermediate bands of both ADDwR and ADDwoR discs for TRAIL and DR5. CONCLUSIONS: TRAIL and DR5 are overexpressed in displaced human TMJ disc, especially in the posterior disc attachment. These results suggest a possible pivotal role of the TRAIL/DR5 system in TMJ disc degeneration.

Proinflammatory cytokines in temporomandibular joint synovial fluid before and after arthrocentesis.

OBJECTIVE: The aim of this study was to evaluate the levels of interleukin (IL)-1beta, IL-6, IL-8, IL-11, and tumor necrosis factor (TNF)-alpha in temporomandibular joint (TMJ) synovial fluid of the patients with internal derangement before and 2 weeks after arthrocentesis. STUDY DESIGN: Forty TMJs of 35 patients (29 females and 6 males, mean age 22.9 years) were included to the study. TMJs were divided into 2 groups: disc displacement with reduction (Group 1, n = 24) and disc displacement without reduction (Group 2, n = 16). Synovial fluid samples were obtained before and 2 weeks after arthrocentesis. IL-1beta, IL-6, IL-8, IL-11, and TNF-alpha concentrations were measured by using specific kits. RESULTS: Two weeks after the arthrocentesis procedures, all cytokines were found to be significantly decreased (P < .05) both in Group 1 and Group 2. The difference between 2 groups was insignificant (P > .05). CONCLUSION: Arthrocentesis is an effective technique for eliminating the studied cytokines from the TMJ synovial fluid.

Anterior fracture-dislocation is more severe than lateral: a biomechanical and neuropathological comparison in rat thoracolumbar spine.

ABSTRACT Fracture-dislocation is one of the most common causes of spinal cord injury (SCI) in human adults, yet it is not widely studied experimentally. Clinical studies have found that anterior fracture-dislocation occurs more commonly and produces greater neurological deficit than lateral fracture-dislocation. However, the effect of loading direction on SCI neuropathology has not been investigated experimentally and the reasons behind these clinical differences are not known. Thoracolumbar vertebrae T12-L1 of anaesthetized rats were dislocated anteriorly or laterally by 9 mm at 220 mm/sec. Spinal cord sections from animals euthanized at 1, 3, and 6 h post-injury, were stained with hematoxylin and eosin (H&E) to detect hemorrhage, the pathologic accumulation of beta-amyloid precursor protein (betaAPP) in white matter axons, and degenerating neurons (Fluoro-Jade and loss of NeuN) in the gray matter. The vertebral fracture load and maximum load were similar for both directions of dislocation; however, vertebral fracture occurred at 4.3 mm (+/-1.5 mm SD) during anterior dislocation compared to 1.1 mm (+/-0.7 mm SD) during lateral dislocation (p < 0.001). betaAPP accumulation and reduction of NeuN immunoreactivity (IR) were greatest along a diagonal band across the spinal cord angled at 45 degrees to the direction of loading (in different planes for each loading direction). Hemorrhage volume (p < 0.05), betaAPP-IR, and reduction of NeuN-IR (p < 0.05 in ventral horns) were more pronounced following anterior dislocation. In addition, there was a different spatial distribution of axonal damage for each direction of dislocation. The findings of this study may explain the greater severity of anterior fracture-dislocation observed clinically and reinforces the need to experimentally model differing human SCIs.

Analysis of estrogen binding sites of the posterior ligament of the human TMJ.

BACKGROUND: Conflicting results have been reported regarding the presence or absence of estrogen-binding sites (EBS) in the human temporomandibular joint (TMJ). The possible role of female sex hormones in the pathophysiology of internal derangement of the TMJ has been suggested to explain the prevalence of TMJ symptoms in female patients. PATIENTS AND METHODS: Posterior bilaminar tissue excised during TMJ articular disc repositioning and posterior ligament repair was taken from 28 patients (26 female, 2 male) for evaluation. Cryosections were stained using a monoclonal antibody (Mab) against EBS. To ensure efficacy of the antibody staining procedure, an internal positive control consisting of human breast tissue previously proven EBS-positive was used. No asymptomatic control TMJ tissue was available for our study. RESULTS: None (0%) of 28 TMJ tissue specimens showed nuclear-staining positive for the presence of EBS in the posterior bilaminar tissue of the TMJ. However, estrogen-binding sites associated with probable inflammatory cells were observed. Our results are consistent with the probability of positives as high as 0.1234 using a 95% confidence interval. CONCLUSIONS: The lack of EBS of the posterior ligament of the TMJ suggests that the role of estrogen contributing to internal derangement of the TMJ appears not to be significant.

Expression of receptor activator of nuclear factor-kappaB ligand in synovial tissue: comparison with degradation of articular cartilage in temporomandibular joint disorders.

OBJECTIVE: The present study was performed to investigate the correlations between expression of the receptor activator of nuclear factor-kappaB ligand (RANKL) in synovial tissue and the degrees of synovitis, degeneration of articular cartilage, and adhesions in patients with internal derangement (ID) of the temporomandibular joint (TMJ). STUDY DESIGN: Expression of RANKL, detected immunohistochemically, and the severity of arthroscopic features (synovitis, degenerative changes of articular eminence, and adhesion) in 30 patients with ID of the TMJ were assessed and the correlations between them were analyzed statistically. RESULTS: RANKL expression was detected in the cytoplasm of synovial lining cells, endothelial cells, and fibroblast cells. However, there were no correlations between RANKL expression in any cell type and the severity of arthroscopic features. CONCLUSION: These observations indicated that the cellular source of osteoclastic differentiation exists in TMJ with ID and may provide insight into the mechanism of osteoclast differentiation.

Prognostic factors in arthrocentesis of the temporomandibular joint: Comparison of bradykinin, leukotriene B4, prostaglandin E2, and substance P level in synovial fluid between successful and unsuccessful cases.

PURPOSE: To compare levels of bradykinin (BK), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and substance P (SP) between successful and unsuccessful cases of arthrocentesis of temporomandibular joint disorders (TMDs). PATIENTS AND METHODS: A total of 66 joints in 66 patients with TMDs who underwent arthrocentesis were evaluated in this study. Synovial fluid diluted with saline solution was aspirated from the superior joint compartment before arthrocentesis and their concentrations of BK, LTB4, PGE2, and SP were determined by enzyme-linked immunosorbent assay. The differences in the detection rate and concentration of each mediator between successful cases and unsuccessful cases of arthrocentesis were analyzed statistically. RESULTS: Arthrocentesis was successful for 77% (51/66) of the joints. The mean detection rate of LTB4 was significantly (P < .05) higher in the unsuccessful cases (47%) than in the successful cases (16%). The mean concentration of BK was significantly (P < .0005) higher in the unsuccessful cases (425 pg/mL) than in the successful cases (144 pg/mL). There was also a statistical correlation between the detection of LTB4 and PGE2 (P < .01). CONCLUSIONS: Increased levels of BK and LTB4 in the synovial fluid of patients with TMDs may indicate that arthrocentesis is less likely to be a successful treatment.

Specific expression of substance P in synovial tissues of patients with symptomatic, non-reducing internal derangement of the temporomandibular joint: comparison with clinical findings.

Our aim was to find out the extent of expression of substance P in synovial tissue from the human temporomandibular joints (TMJ) with symptomatic, non-reducing internal derangement, and to investigate the relationship between substance P and clinical findings. Fifty-four joints in 54 patients were examined immunohistochemically. Specimens of synovial tissue from 10 joints in 8 subjects with habitual dislocation of the TMJ with no pain were examined as controls. Cells that stained for substance P were found mainly among the endothelial cells in the blood vessels beneath the lining cells in synovial tissues from 47 of the 54 joints (87%) with internal derangement and from 5 of the 10 control joints. The extent score of cells that stained for substance P in joints with internal derangement was significantly higher than that in controls (p=0.02). The extent score of these cells did not correlate with pain in the joint or the degree of synovitis. These results suggest that substance P may have some roles in both the physiological and pathological conditions in patients with symptomatic internal derangement of the TMJ.

Inflammatory cytokines correlated with clinical outcome of temporomandibular joint irrigation in patients with chronic closed lock.

OBJECTIVE: This study investigated the correlation of clinical outcomes of temporomandibular joint (TMJ) irrigation with the occurrence and concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-12, and IL-10 in the washed-out synovial fluid (SF) in patients with chronic closed lock (CCL) of the TMJ. STUDY DESIGN: Thirty-six patients underwent a visually guided TMJ irrigation (VGIR). SF samples were collected immediately before VGIR. The patients were divided into either successful (s-group; n = 25) or unsuccessful groups (u-group; n = 11). The detection rates and concentrations of each cytokine per milligram of total protein in the SF were measured, and then compared between the s- and u-groups. RESULTS: All of the investigated cytokines were detectable with various rates, concentrations, and combination patterns. The detection rate and concentrations of IL-6 were significantly higher in the u-group, and those of IL-10 were significantly higher in the s-group. CONCLUSIONS: The investigated cytokines were suggested to be involved in the pathophysiology of TMJ CCL. The results also suggest that IL-6 in the SF is an indicator of an unsuccessful outcome, and that IL-10 is a significant predictor of a successful outcome of TMJ irrigation for CCL.