Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis

Objective: To determine whether all-trans-retinoic acid (ATRA) improves the destruction of joints and the effect of cytokines on DBA/1J mice with collagen-induced arthritis (CIA). Methods: Starting from the time of type II collagen injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA 3 times per week for 35 days. The effects of treatment were monitored by determining arthritis and histological scores and measuring cellular proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3. Results: The arthritis score and incidence of arthritis were lower in the mice treated with ATRA than in those treated with PBS. Histopathologic evidence of joint damage was 34% lower, and the infiltrations of macrophages were reduced in the mice treated with ATRA compared with those treated with PBS. Type II collagen- and ConA-stimutated proliferation of spleen cells, the production of cytokines (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti-collagen antibodies, and the expression of mRNAs for MCP-1 were significantly reduced in the mice treated with ATRA than in those treated with PBS. Conclusion: ATRA improved the clinical course and reduced the production of inflammatory cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that ATRA might be also effective for the treatment of inflammatory arthritis like human rheumatoid arthritis. (c) 2005 Elsevier Inc. All rights reserved.