Role of transforming growth factor beta in the pathophysiology of chronic inflammation

Transforming growth factor beta (TGF-beta), a cytokine identified in acute and chronic inflammatory sites, mediates leukocyte recruitment and activation essential to the development of such lesions. Released by platelets upon aggregation and by leukocytes stimulated with bacterial products or inflammatory mediators, TGF-beta has potent chemotactic activity for blood neutrophils, monocytes, and lymphocytes. By augmenting integrin expression, TGF-beta facilitates leukocyte adhesion to the vessel wall and extracellular matrix at the site of inflammation. Once within the inflammatory site, mononuclear cells are stimulated by TGF-beta to release cytokines important in the network of molecules regulating 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 pathogenesis has been demonstrated. Administration of anti-TGF-beta to sites of chronic destructive inflammation not only blocked leukocyte recruitment and activation, but also inhibited the subsequent destruction of bone and cartilage characteristics of such lesions.