SOLUBLE IL-15 RECEPTOR ALPHA-CHAIN ADMINISTRATION PREVENTS MURINE COLLAGEN-INDUCED ARTHRITIS - A ROLE FOR IL-15 IN DEVELOPMENT OF ANTIGEN-INDUCED IMMUNOPATHOLOGY

IL-15 has recently been detected in the synovium of patients with rheu matoid arthritis. IL-15-activated T cells induce significant TNF-alpha synthesis by macrophages via a cell contact-dependent mechanism, sugg esting a key regulatory role for IL-15, Here, we report that the admin istration of a soluble fragment of IL-15R alpha into DBA/1 mice, profo undly suppressed the development of collagen-induced arthritis. This w as accompanied in vitro by marked reductions in Ag-specific proliferat ion and IFN-gamma synthesis by spleen cells from treated mice compared with control mice and in vivo by a significant reduction in serum ant i-collagen Ab levels. These data directly demonstrate a pivotal role f or IL-15 in the development of inflammatory arthritis and also suggest that antagonists to IL-15 may have therapeutic potential in rheumatic diseases.