Evaluation of the level of preinlammatory cytokines(IL-1ß and TNF-?) and anti inflammatory cytokines (IL-4 and IL-10) in rheumatoid arthritis and chronic periodontitis patients

Periodontitis is a chronic inflammatory disease characterized by loss of the periodontal ligament and alveolar bone, and is a major cause of tooth loss. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation that results in destruction of joint tissues. Chronic periodontitis (CP) has been linked to a variety of systemic medical disorders, including coronary artery disease, osteoporosis and low birth weight, in most cases there is no obvious common disease mechanism even though some shared and potentially pathogenic associations, such as C-reactive protein, have been identified. On the other hand, chronic periodontitis and rheumatoid arthritis are remarkably parallel disease processes that share not only same clinical features, but also pathophysiologic, epidemiological and therapeutic features. The loss of bone and connective tissue in periodontitis, as well as in the synovial joint with RA, is mainly consequence of increased local tissue destruction, for instance, a disturbed balance between tissue formation and degradation. Cytokines participate in the regulation of this process. The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-?) and interleukin (IL)-1ß are important promoters of bone resorption in both diseases. In addition to that, the lack of anti-inflammatory cytokines such as IL-4 and IL-10 may contribute the initation and progression of inflammation during chronic synovitis in RA joints. The balance between pro-inflammatory and anti-inflammatory cytokines may be crucial for determining the immunopathology of KP and RA.Therefore, this study aimed to investigate the levels of pro-inflammatory cytokines (IL-1ß and TNF-?) and anti-inflammatory cytokines (IL-4 and IL-10) in gingival crevicular fluid (GCF) and serum in CP and RA patients. Furthermore, the correlations between the clinical parameters and the levels of cytokines and the pro-inflammatory/anti-inflammatory cytokine ratio have been evaluated. Forty nine subjects including 17 RA, 16 CP and 16 controls were enrolled. Full mouth periodontal parameters including probing depths (PD), gingival index (GI), plaque index (PI), gingival recession (REC) and clinicalviiattachment loss (CAL) were measured at six sites for each tooth. GCF samples were collected from six maxillary anterior sites per patients and analyzed for IL-1ß, TNF-?, IL-4 and IL-10 by an enzyme-linked immunosorbent assay (ELISA). 5cc blood samples were obtained from all participants and serum was aliquoted after centrifugation. Serum samples were analyzed for IL-1ß and IL-10 by an enzyme-linked immunosorbent assay. Control subjects exhibited lower total amounts of IL-1ß and IL-4 in GCF samples compared with both RA and CP groups. Moreover, the control group had significantly higher concentrations IL-10 compared to other groups. The total amount of TNF-? in GCF was lower in RA subjects. The serum concentration and the total amount of IL-1ß were higher in RA group, while the serum concentrations of IL-10 were not different among the groups. The pro-inflammatory (IL-1ß+TNF-?)/anti-inflammatory (IL-4+IL-10) GCF ratio did not differ among the groups, where the IL-1ß/ IL-10 GCF ratio was lower in the control group. However, in serum concentrations the lowest IL-1ß/ IL-10 ratio was detected in RA group. IL-1ß/ IL-4 and TNF-?/ IL-10 GCF ratios were not significantly different among the three groups. The TNF- ?/ IL-4 GCF ratio was lower in the CP group compared with RA and control groups. In RA group, negative correlation was found between full mouth plaque index and IL-4 GCF concentrations and IL-4 GCF total amounts. Also strong positive correlations between pro-inflammatory (IL-1ß+TNF-?)/anti-inflammatory (IL-4+IL-10) GCF ratio and plaque index were found in this group. In CP group, negative correlation between probing depth and IL-4 GCF concentration was found. An imbalance between pro-inflammatory and anti-inflammatory cytokines plays an important role in both diseases. Future studies should aim to investigate the mechanism of interactions between pro-inflammatory and anti-inflammatory cytokine production at molecular and cellular levels at different stages of periodontal lesions in both CP and RA patients.viiiKey Words: Chronic periodontitis, rheumatoid arthritis, interleukin-1beta, tumor necrosis factor-alpha, interleukin-4, interleukin-10, gingival crevicular fluid.