IMPORTANT IMMUNOREGULATORY ROLE OF INTERLEUKIN-11 IN THE INFLAMMATORYPROCESS IN RHEUMATOID-ARTHRITIS

Objective. To investigate the possible immunoregulatory role of interl eukin-11 (IL-11) in rheumatoid arthritis (RB). Methods. IL-11 protein was assayed in RA tissue, and the effect of exogenous IL-11 on neutral ization of endogenous IL-11 was investigated with respect to tumor nec rosis factor alpha (TNF alpha), matrix metalloproteinase (MMP), and ti ssue inhibitor of metalloproteinases (TIMP) production. Results. IL-11 was found in RA synovial membranes, synovial fluids, and blood sera. Blockade of endogenous IL-11 resulted in a 2-fold increase in TNF alph a levels, which increased to 22-fold if endogenous IL-10 was also bloc ked. Addition of exogenous IL-11 inhibited spontaneous TNF alpha produ ction in RA synovium only in the presence of soluble IL-11 receptor. H owever, exogenous IL-11 directly inhibited spontaneous MMP-1 and MMP-3 production, and up-regulated TIMP-1 in RA synovial tissue. Conclusion . IL-11 has important endogenous immunoregulatory effects in RE synovi um, which suggests that exogenous IL-11 may have therapeutic activity in RA.