TRANSFORMING GROWTH-FACTOR BETA-1 SUPPRESSES ACUTE AND CHRONIC ARTHRITIS IN EXPERIMENTAL-ANIMALS

Systemic administration of the cytokine, TGF-beta-1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF-beta-1 administration (1 or 5-mu-g/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs. 11; P < 0.025) and the chronic phase (AI = 0 vs. 12.5) of the disease. Moreover, TGF-beta-1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease. Histopathological examination of the joint revealed the systemic TGF-beta-1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF-beta-1 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF-beta-1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment. These observations not only provide insight into the immunoregulatory effects of TGF-beta, but also implicate this cytokine as a potentially important therapeutic agent.