An update on the cytokine network in RA

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Curr Opin Rheumatol. 2004 May;16(3):218-222.

An update on the cytokine network in rheumatoid arthritis.

Miossec P.

Department of Immunology and Rheumatology, Hopital Edouard Herriot,

Lyon, France.

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.

PMID: 15103248

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