INHIBITION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY SK-AND-F-98625 A COA-INDEPENDENT TRANSACYLASE INHIBITOR, IN CULTURED RAT PERITONEAL-MACROPHAGES

When rat peritoneal macrophages were incubated in medium containing th apsigargin, tumor necrosis factor-alpha (TNF-alpha) production was inc reased time-dependently. In the presence of SK&F 98625, a CoA-independ ent transacylase inhibitor, the thapsigargin-induced TNF-alpha product ion was inhibited dose-dependently. Platelet-activating factor (PAF) a nd prostaglandin E2 (PGE2) production were also inhibited by SK&F 9862 5. The SK&F 98625-induced inhibition of TNF-alpha production was not p revented by addition of PGE2. PAF antagonists such as E6123, L-652,731 and CV-6209 partially inhibited the thapsigargin-induced TNF-alpha pr oduction, suggesting that concurrently produced PAF in thapsigargin-st imulated macrophages up-regulates TNF-alpha production. The inhibition by SK&F 98625 of thapsigargin-induced TNF-alpha production might be p artly due to the inhibition of PAF production. (C) 1998 Elsevier Scien ce Inc.