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

Abstract

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.

Fig. 1

The levels of IL-12 in paired sera and synovial fluid (SF) obtained simultaneously from patients with RA (•; n = 53) and osteoarthritis (○; OA) (n = 22). Broken line indicates the limit of detectable concentration of IL-12 (5 pg/ml). Bars represent median levels. Comparison of median IL-12 levels between sera and SF was performed using paired Wilcoxon signed ranks test. NS, Not significant.

Fig. 2

Correlations of IL-12 levels with tender or swollen joint scores in 104 patients with RA. —-, •, Tender joint scores; – – – – –, ○, swollen joint scores.

Fig. 3

Changes of IL-12 levels 4 months after treatment compared with baseline in (a) improved (n = 26) versus (b) non-improved patients (n = 31) with RA.

Fig. 4

Correlations of IL-12 levels with IL-6 and tumour necrosis factor-alpha (TNF-α) levels in synovial fluid of RA (n = 53). —–, •, TNF-α; – – – – –, ○, IL-6.