Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals.

Abstract

Systemic administration of the cytokine, TGF,f1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF,81 administration (1 or 5 ,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 (Al = 0 vs. 12.5) of the disease. Moreover, TGF,61 suppressed the evolution of arthritis even when administration was begun after the acute phase ofthe disease. Histopathological examination of the joint revealed the systemic TGF,81 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF,81 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF,&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#, but also implicate this cytokine as a potentially important therapeutic agent. (J. Clin.

Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease

“…TGF-β1 administration to mice protects against collagen-induced arthritis and relapsing experimental allergic encephalomyelitis [36][37][38][39] . T-cell suppression of experimental autoimmune encephalomyelitis after oral tolerization to myelin basic protein seems to be mediated by TGF-β1 (ref.…”

Dynamic expression of transforming growth factor-betas (TGF-β) and their type I and type II receptors in the synovial tissue of arthritic rats

“…To date, it has been shown that systemic administration of TGF-1 to rodents protects against induction of arthritis [12,13] and experimental allergic encephalomyelitis (EAE) [37][38][39][40]. It has also been demonstrated that TGF-2 is as effective as TGF-1 in protecting against EAE [40,41], thus indicating that these TGF-s have similar biological effects in EAE.…”

“…Several studies have demonstrated the presence of TGF-in the synovium and synovial fluids of RA patients [5][6][7][8][9][10][11]. In rodents, conversely, the action of TGF-or its antagonists administered in vivo in experimental arthritis has been intensively studied [12,13]. However, in the animal arthritis models, little is known concerning both the distribution and the kinetics of the different isoforms of TGF-and its receptors [8].…”

ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

“…29 Our results are also supported in light of the traditional view that TGF-b plays a protective role in matrix metabolism. 30,31 Moreover, TGF-b has been described to inhibit IL1-b-induced chondrocyte protease activity and cartilage proteoglycan degradation, and promote proteoglycan synthesis in cartilage. 32 However, our data point out that the balance between the catabolic versus anabolic stimuli provided by proinflammatory cytokines and TGF-b3, observed in the presence of 1 ng=mL of both cytokines, is unstable.…”