Antioxidant activities and redox regulation of interferon-gamma-induced tryptophan metabolism in human monocytes and macrophages.

This article summarises studies supporting the proposal that induction of L-tryptophan (Trp) degradation along the kynurenine pathway in human monocytes and macrophages by interferon-gamma (IFN gamma) represents a novel extracellular antioxidant defence that acts to prevent inadvertent oxidative damage to host tissue during inflammation. The studies show that formation and release of the aminophenolic antioxidant 3-hydroxyanthranilic acid (3-HAA) is responsible for the ability of IFN gamma-primed human macrophages to inhibit the oxidation of low density lipoprotein (LDL); an event implicated as an important event in atherogenesis. 3-HAA efficiently inhibits LDL oxidation by acting as an aqueous oxidant scavenger and a synergist for LDL-associated vitamin E. Indoleamine 2,3-dioxygenase activity (IDO) is the initial and rate limiting enzyme of Trp degradation along the kynurenine pathway. Nitric oxide inhibits IDO activity in IFN gamma-primed human macrophages and this may represent a physiological regulatory mechanism of the dioxygenase during inflammation.