Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by local application of human recombinant IL-1β, IL-2 and IL-6

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