TRANSFORMING GROWTH-FACTOR-BETA-1 REGULATION OF MACROPHAGE ACTIVATIONDEPENDS ON THE TRIGGERING STIMULUS

We have examined the effects of transforming growth factor beta1 (TGF- beta1) on the regulation of murine bone marrow-derived macrophage func tion. TGF-beta, added simultaneously with or up to 4 h before interfer on-gamma (IFN-gamma) plus lipopolysaccharide (LPS), inhibited macropha ge leishmanicidal activity, nitrite (NO2-) production and secretion of prostaglandin E2. In contrast, no effect of TGF-beta could be demonst rated on macrophages stimulated with IFN-gamma plus tumor necrosis fac tor-alpha (TNF-alpha) under the same conditions. These results suggest ed that TGF-beta inhibited LPS-induced triggering of macrophage activa tion, which was confirmed by studies with IFN-gamma-primed cells. Inte restingly, when macrophages were pretreated with TGF-beta for 24 h, NO 2- production in response to IFN-gamma plus TNF-alpha was also inhibit ed. Although control and IFN-gamma/LPS-stimulated macrophages were fou nd to secrete latent TGF-beta, only the IFN-gamma/LPS cultures produce d biologically active TGF-beta. Significantly, active TGF-beta was pre sent at concentrations shown earlier to inhibit macrophage function.