Lipid mediator interplay: resolvin D1 attenuates inflammation evoked by glutathione-conjugated lipid peroxidation products.

Non-enzymatic oxidation of cellular lipids, one of the characteristic features of inflammation, leads to formation of highly reactive and toxic alpha,beta-unsaturated aldehydes, such as 4-hydroxy-trans-2-nonenal (HNE). Conjugation of HNE with reduced glutathione (GS-HNE) is widely believed to represent a form of detoxification. The study by Spite et al. in the current issue of the British Journal of Pharmacology shows that glutathiolation of HNE confers potent pro-inflammatory properties on this alpha,beta-unsaturated aldehyde. They find that GS-HNE directly activates human neutrophil granulocytes in vitro and evokes peritonitis in mice. Pre-treatment with resolvin D1, which is derived from omega-3 fatty acids, markedly attenuated the peritoneal leukocyte accumulation and production of prostaglandins and leukotrienes induced by GS-HNE. Their findings have profound implications for the analysis of inflammation in describing the generation of a novel class of pro-inflammatory mediators, through glutathione-dependent metabolism of lipid-peroxidation products, and emphasize the therapeutic potential of resolvin D1 in inflammatory diseases.