PROINFLAMMATORY CYTOKINE PRODUCTION AND CARTILAGE DAMAGE DUE TO RHEUMATOID SYNOVIAL T-HELPER-1 ACTIVATION IS INHIBITED BY INTERLEUKIN-4

Objectives-To investigate the role of T helper-1 cell (Th1) activation in the induction of proinflammatory cytokine production and cartilage damage by rheumatoid arthritis (RA) synovial fluid mononuclear cells (SFMNC) and the subsequent possible beneficial role of the T helper-2 cell (Th2) cytokine interleukin-4 (IL-4) in the inhibition of this pro cess. Methods-SFMNC were stimulated with bacterial antigen (hsp60) to activate Th1 cells. Th1 and Th2 specific cytokine profiles (interferon gamma (IFN gamma) and IL-4) and proinflammatory cytokines interleukin -1 (IL-1) and tumour necrosis factor alpha (TNF alpha) in the conditio ned media were analysed. In addition, the conditioned media were teste d for their ability to induce cartilage damage. The same parameters we re measured in the presence of IL-4. Results-Stimulation of SFMNC with bacterial antigen resulted in an increase in IFN gamma, IL-1, and TNF alpha production which was accompanied by the induction of cartilage damage. Th1 activation could be inhibited by IL-4 as shown by a reduct ion of IFN gamma. This was accompanied by a decrease in IL-1 and TNF a lpha production and inhibition of cartilage damage. Conclusions-Th1 ac tivation is a possible mechanism by which inflammation in RA joints is enhanced. The Th2 cytokine IL-4 inhibits this Th1 activity and may di minish inflammation and induction of cartilage damage in RA joints.