AVAROL RESTORES THE ALTERED PROSTAGLANDIN AND LEUKOTRIENE METABOLISM IN MONOCYTES INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Infection of monocytes with human immunodeficiency virus type 1 (HIV-1) (strain Ada-M) caused increased levels of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in vitro. These two products result from the activities of the two enzymes cyclooxygenase and 5-lipoxygenase. The addition of the sesquiterpenoid hydroquinone Avarol, an HIV inhibitor, strongly reduced the levels of LTB4 and PGE2 via inhibition of both cyclooxygenase and lipoxygenase in monocytes. The 50% inhibition concentrations (IC50) for the enzymes were determined to be 2.26-mu-M (cyclooxygenase) and 1.97-mu-M (lipoxygenase). A 50% reduction of the extent of PGE2 and LTB4 production in HIV-infected monocytes was measured at a concentration of 0.9-mu-M Avarol, a dose which caused an 80% anti-HIV effect in vitro (50% inhibition of virus release from infected cells: 0.3-mu-M). We conclude that Avarol inhibits the enzymes cyclooxygenase and lipoxygenase and suggest that. in general, inhibitors of these enzymes are promising anti-HIV compounds.