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-i cell (Thl) 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 ofthis process. Methods-SFMNC were stimulated with bacterial antigen (hsp6O) to activate Thl cells. Thl and Th2 specific cytokine profiles (interferon gamma (IFNγ) and IL-4) and proinflammatory cytokines interleukin-l (IL-1) and tumour necrosis factor α (TNFα) in the conditioned media were analysed. In addition, the conditioned media were tested for their ability to induce cartilage damage. The same parameters were measured in the presence of IL-4. Results-Stimulation of SFMNC with bacterial antigen resulted in an increase in IFNyγ IL-1, and TNFα production which was accompanied by the induction of cartilage damage. Thl activation could be inhibited by IL-4 as shown by a reduction of IFNy. This was accompanied by a decrease in IL-1 and TNFa production and inhibition of cartilage damage. Conclusions-Thl activation is a possible mechanism by which inflammation in RA joints is enhanced. The Th2 cytokine IL-4 inhibits this Thl activity and may diminish inflammation and induction of cartilage damage in RA joints.