MODULATION OF HU MU SEVERE COMBINED IMMUNODEFICIENT (SCID) MOUSE ARTHRITIS BY LOCAL APPLICATION OF HUMAN RECOMBINANT IL-1-BETA, IL-2 AND IL-6/

The contribution of interleukins produced by most inflammatory cells t o chronic arthritis is not well understood. Therefore, we investigated the influence of several human recombinant interleukins (IL-1 beta, I L-2 and IL-6) on joint swelling, on the inflammatory process, and on s erological parameters in a novel animal model of arthritis, the human/ murine SCID arthritis. In this model an arthritis is induced by implan ting human synovial tissue from patients with rheumatoid arthritis (RA ) into the knee joint of mice with SCID. These mice tolerate the xenog eneic implant and develop a mixed human/murine pannus tissue. The inte rleukins were injected daily for 7 or 14 days after implantation. IL-I beta led to a significant increase in joint swelling. It intensified the inflammatory process accompanied by enhanced migration of murine i nflammatory cells into the knee joint. The production of human IL-6 in the transplanted tissue was stimulated through the application of IL- 1 beta, and the serum level of human IL-6 was thus significantly highe r than in controls. We could not observe a significant influence of IL -1 beta on the production of human IgG or IgM by the implant. The appl ication of human IL-2 had a weak effect similar to that of IL-1 beta, but without statistical significance. Although IL-6 is a good marker f or inflammation in RA, the application of recombined human 1L-6 had no influence on the inflammatory process in this model.