Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis

The co-ordinate role of the Th1 cytokine IL-12 and the proinflammatory cyto kine TNF in arthritis was explored using the DBA/1 mouse model, collagen-in duced arthritis (CIA). In this study, mice with established arthritis were treated with anti-IL-12 and/or anti-TNF antibodies for 10 days from the ons et of disease. Clinical assessment showed that the combined antibody treatm ent ameliorated disease severity to a greater extent than anti-TNF alone. S upporting these observations, histological analysis revealed that there was a reduced joint damage in the mice that received combined anti-IL-12 and a nti-TNF treatment, compared to the other treatment groups. Anti-IL-12 had n o statistically significant effect on the clinical outcome of disease. The combination of anti-IL-12 and anti-TNF treatment was found to reduce collag en type II (CII)-specific lymph node cell IFN-gamma production and prolifer ation, as well as decrease the anti-CII IgG2a:IgG1 ratio more effectively t han either treatment alone. When the antibodies were added to synovial cell s from arthritic mice and bone marrow macrophages in vitro, anti-TNF dimini shed IL-12 production, but anti-IL-12 had no effect on TNF production. Thes e data suggest that, through the partial regulation of IL-12, TNF modulates the immune response in arthritis, as well as the inflammatory response; Th e synergistic action of anti-TNF and anti-IL-12 on CIA may provide a new th erapeutic approach for treating rheumatoid arthritis.