The role of IL‐12 in inflammatory activity of patients with rheumatoid arthritis (RA)

The aim of this study was to investigate the role of IL‐12 in patients with RA. IL‐12 (p70) and its associated cytokines were measured in sera and synovial fluid (SF) using an enzyme‐linked immunosorbent method. Seven American College of Rheumatology (ACR) core set measures as well as IL‐12 levels were sequentially monitored at the commencement and 4 months after treatment with a low‐dose steroid and disease‐modifying anti‐rheumatic drugs (DMARDs). In sera, 64 (42.2%) of 152 RA patients had detectable concentrations of IL‐12 (p70), whereas one (1.4%) of 69 osteoarthritis (OA) patients and five (10%) of 50 healthy controls had detectable IL‐12 ( P  < 0.001). The median level of circulating IL‐12 was also higher in RA patients ( P  < 0.001). In SF, the number of patients with detectable IL‐12 and the median IL‐12 levels were significantly higher in RA patients ( n  = 53) than in OA patients ( n  = 22). In paired samples ( n  = 53) of sera and SF from RA patients, IL‐12 levels were higher in the SF than in sera ( P  < 0.001). Patients with detectable IL‐12 ( n  = 51) in sera had higher tender joint scores ( P  = 0.003), swollen joint scores ( P  < 0.001) and C‐reactive protein (CRP; P  = 0.036), than those without ( n  = 55). Four months after treatment with DMARDs, the improved group showed a larger IL‐12 decrease than the non‐improved group ( P  = 0.017). The levels of IL‐12 correlated positively with those of IL‐2, interferon‐gamma, IL‐6, and tumour necrosis factor‐alpha, but were correlated inversely with those of IL‐10. Our results demonstrate that IL‐12 levels reflect RA disease activity and that IL‐12 is involved in the production of proinflammatory cytokines. An IL‐12 blockade could be useful for the treatment of RA.