INTERLEUKIN-6 REDUCES CARTILAGE DESTRUCTION DURING EXPERIMENTAL ARTHRITIS - A STUDY IN INTERLEUKIN-6-DEFICIENT MICE

Using interleukin (IL)-6-deficient (IL-6%) mice or wild-type mice, we investigated the controversial role of IL-6 in joint inflammation and cartilage pathology during zymosan-induced arthritis (ZIA), Monoarticu lar arthritis was elicited by injection of zymosan into the right knee joint cavity, Production of lL-1, tumor necrosis factor (TNF), IL-6, and nitric oxide by the inflamed knee was assessed in washouts of join t capsule specimens, Plasma corticosterone was measured using a radioi mmunoassay. Proteoglycan synthesis was assessed using [S-35]sulfate in corporation into patellas ex viva Joint swelling was quantified by joi nt uptake of circulating (99m)Technetium pertechnetate, Histology tons taken to evaluate cellular infiltration and cartilage damage, Zymosan caused a rapid increase in articular IL-I, IL-6, TNF, and NO levels, Except for IL-6, the released amounts and time coarse of these mediato rs were comparable ill the IL-6-deficient mice and the wild-type mice Elevated plasma corticosterone levels were measured during the first d ay of arthritis in both strains. At day 2 of ZIA, joint inflammation ( joint swelling and cell exudate) in IL-6-deficient mice was comparable with that in the wild-type mice. The marked suppression of chondrocyt e proteoglycan synthesis and proteoglycan degradation were on the aver age higher in the IL-6-deficient mice, Together this resulted in a mor e pronounced proteoglycan depletion in the IL-G-deficient mice as comp ared with the wild-type mice during the first week of arthritis, Injec tion of recombinant IL-6 into the joint cavity, corrected the IL-6 def iciency and significantly reduced cartilage destruction. Inflammation was more chronic in the wild-type mice, and these mice also showed a h igher prevalence for osteophyte formation. In ZIA, IL-6 plays a dual r ole in connective tissue pathology, reducing proteoglycan loss in the acute phase and enhancing osteophyte formation in the chronic phase. T he latter could be related to the more severe joint inflammation as se en in the normal (IL-6-producing) animals during the chronic phase of arthritis.