Purpose of review: To update the knowledge accumulated on the contribution of cytokines to rheumatoid arthritis and related animal models. Publications from the end of 2002 and 2003 period were analyzed for a selection.
Recent findings: A better understanding of the clinical results with tumor necrosis factor-alpha inhibitors has come from studies in treated patients. The expected effect of infliximab on the apoptosis of cells expressing tumor necrosis factor-alpha was not observed in synovium biopsy specimens. The mode of action of tumor necrosis factor-alpha on bone destruction has been clarified in gene-defective mice. Tumor necrosis factor-alpha acts through osteoclasts--an effect that is inhibited with osteoprotegerin. New interleukin-1 inhibitors with a potential for increased efficacy, such as interleukin-1trap, have been manufactured and are now being tested in rheumatoid arthritis. The list of cytokines of interest for therapeutic intervention has been growing rapidly. The results with animal models have provided clues to control arthritis with natural interleukin-18 inhibitors, such as interleukin-18 BP. Additional results have been accumulated that indicate the contribution of T cell subsets in inflammation and destruction through the production of interleukin-17. Synergistic interactions with other cytokines are critical in the interleukin-17 tuning effects. Macrophage inhibitory factor was described many years ago. Its comeback is based on properties of synoviocyte activation and proliferation.
Summary: Such findings are critical for a better understanding of response heterogeneity in patients treated with the cytokine inhibitors now on the market. New therapeutic approaches are been planned from these results.