REGULATORY ROLE OF INTERLEUKIN-10 IN JOINT INFLAMMATION AND CARTILAGEDESTRUCTION IN MURINE STREPTOCOCCAL CELL-WALL (SCW) ARTHRITIS - MORE THERAPEUTIC BENEFIT WITH IL-4 IL-10 COMBINATION THERAPY THAN WITH IL-10 TREATMENT ALONE/

Interleukin 10 (IL-10) and IL-4 are important downregulators of a numb er of macrophage functions. The authors investigated the role of endog enous IL-4 and IL-10 and the therapeutic effect of addition of these c ytokines on joint inflammation and cartilage destruction in the early stages of the macrophage dependent murine streptococcal cell wall (SCW ) arthritis model, It was demonstrated that endogenous IL-10, but not IL-4, plays a pivotal role in the regulation of SCW arthritis. Blockin g endogenous IL-10 with anti-IL-10 antibodies resulted in a sustained arthritis with more dense synovial infiltrate as well as enhanced cart ilage damage. Adding exogenous IL-10 further enlarged the suppressive effect of endogenous LL-IO, Even more pronounced amelioration was foun d with the combination IL-4/IL-10, This resulted in a reduced swelling and a restorative overshoot in chondrocyte proteoglycan synthesis at day 4 (140%), Treatment with the combination IL-4/IL-10 not only a mar ked reduction of tumour necrosis factor alpha (TNF-alpha) levels, like IL-10 treatment alone, but also the IL-1 beta levels were strongly re duced in the synovium, In conclusion, the data is consistent with a do minant role of TL-IO in natural suppression of arthritis expression, w hereas combined treatment with IL-4 and IL-10 appears to be of potenti al therapeutic value. (C) 1998 Academic Press Limited.