Immunoregulation of Proteoglycan-Induced Arthritis in Balb/c Mice.
Immunization of BALB/c mice with a select group of cartilage proteoglycans induces progressive polyarthritis. The pathological mechanisms of proteoglycan-induced arthritis are based on autoimmune reactions developed against the mouse self-proteoglycan. This autoimmune inflammatory animal model, which shows many similarities to human rheumatoid arthritis, has close to 100% incidence in susceptible BALB/c mice and is an excellent in vivo model for testing disease-modifying agents. The aim of this work was to study the regulatory mechanisms which control the autoimmune reactions in proteoglycan-induced arthritis, in association with the release of most important cytokines/mediators (interleukin 1 (IL-1), interleukin-2 [IL-2], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-alpha], and prostaglandin E(2)) which are believed to play key roles in inflammatory events and cartilage degredation. We have found relatively high levels of IL-1 sera and synovial-cell culture supernatants of arthritic animals, whereas IL-1 was not detected in nonarthritic control animals. Serum autoantibody and IL-1 levels seemed to be sensitive indicators of the oncoming inflammatory events in the joints, whereas autoreactive T-cell responses to mouse proteoglycan became evident only after the onset of arthritis. As proteoglycan-specific T-cell responses were mainly restricted to the joint-draining lymph nodes during the arthritic process, it is likely that the autoantigen-driven mechanism of joint inflammation became local and self-sustaining during cartilage degradation. Thus, autoimmune mechanisms seem to be essential in the "organ specificity" of inflammatory reactions, as "arthritogenic" lymphocytes migrate to and accumulate in both the lymphoid organs and the synovium. IL-1 and IL-2 are among the most important mediators in proteoglycan-induced arthritis and are able to influence autoimmune reactions and the migration of lymphocytes to the synovium.
Mikecz
Katalin
K
Departments of Orthopedic Surgery and Biochemistry, Rush Medical College, Rush--Presbyterian--St. Luke's Medical Center, Chicago, USA.
Glant
Tibor T.
TT