RAPID ONSET SYNOVIAL INFLAMMATION AND HYPERPLASIA INDUCED BY TRANSFORMING GROWTH FACTOR-BETA

After intraarticular injection of TGF-β1 or TGF-β2, marked swelling and erythema of the injected joints were apparent within 12-24 h. On a scale of 0 to 4, by day 3, the TGF-β-treated joints had articular indices (AI) of 3.6 ± 0.5 to 4.0 ± 0.0 compared with no response for the vehicle-injected contralateral joints. Histopathologic evaluation revealed a predominantly mononuclear phagocyte infiltrate with some neutrophils and T lymphocytes, consistent with active inflammation. The monocytic pattern of leukocyte infiltration at 2-3 d was comparable to that seen in animals with antigen-induced arthritis after 2-3 wk. Extensive synovial fibroblast hyperplasia became apparent within 48 h, likely as a result of TGF-β induction of growth factor synthesis by the accumulating monocytes. TGF-β2, a homologue of TGF-β1, was found to induce a similar level of synovitis and synovial hyperplasia consistent with its parallel monocyte and fibroblast chemotactic properties and ability to induce transcription and translation of monocyte/macrophage-derived groth factors. These data suggest that TGF-β, released by platelets and activated inflammatory cells, may play a direct role in leukocyte recruitment and activation in arthritic and other chronic inflammatory lesions.