PROSTAGLANDIN AND NITRIC-OXIDE REGULATE TNF-ALPHA PRODUCTION DURING TRYPANOSOMA-CRUZI INFECTION

The mechanisms that control TNF-alpha production by macrophages during Trypanosoma cruzi infection are still unknown. Destruction of intrace llular forms by cytokine activated macrophages is considered to be a m ajor mechanism of parasite elimination. Although in vitro TNF-alpha co ntributes to enhanced parasite destruction by macrophages, previous wo rk in vivo has shown that as the parasite burden increases, serum TNF- alpha levels decline. In this report we show that TNF-alpha production by peritoneal adherent cells is elevated at the initial phase of T. c ruzi infection. As infection progresses TNF-alpha production decreases . The observed reduction is partly due to inhibition, largely exerted by endogenous PG and secondarily by NO. Inhibition of their synthesis partially restored the ability to produce high levels of TNF-alpha to macrophages upon stimulation by LPS. Neither endogenous IL-10 nor TGF- beta seem to be involved in the negative regulation of TNF-alpha produ ction. (C) 1998 Elsevier Science B.V. All rights reserved.