ROLE OF TRANSFORMING GROWTH-FACTOR-BETA IN THE PATHOPHYSIOLOGY OF CHRONIC INFLAMMATION

TRANSFORMING GROWTH FACTOR BETA (TGF-beta), a cytokine identified in a cute and chronic inflammatory sites, mediates leukocyte recruitment an d activation essential to the development of such lesions. Released by platelets upon aggregation and by leukocytes stimulated with bacteria l products or inflammatory mediators, TGF-beta has potent chemotactic activity for blood neutrophils, monocytes, and lymphocytes. By augment ing integrin expression, TGF-beta facilitates leukocyte adhesion to th e vessel wall and extracellular matrix at the site of inflammation. On ce within the inflammatory site, mononuclear cells are stimulated by T GF-beta to release cytokines important in the network of molecules reg ulating the host response to microorganisms and immunologic challenge. Thus, bacteria and their products, in addition to directly recruiting and activating leukocytes at sites of infection, indirectly influence these events through the induction of cytokines such as TGF-beta. By antagonizing the activity of TGF-beta with neutralizing antibodies, a causal relationship between this cytokine, inflammation, and pathogene sis has been demonstrated. Administration of anti-TGF-beta to sites of chronic destructive inflammation not only blocked leukocyte recruitme nt and activation, but also inhibited the subsequent destruction of bo ne and cartilage characteristic of such lesions.