Leukotriene B₄: agonist for the fat regulator PPARα

Abstract

Control of an inflammatory response is primarily achieved by ‘turning off’ or inactivating the signals that help to recruit cells of the immune system to the site of inflammation. Many inflammatory disorders underscore the importance of turnover of signals including the broad set of arachidonic acid metabolites. One such fatty acid derivative, leukotriene B₄(LTB₄) is a potent chemotactic agent whose activity is mediated by a membrane receptor¹. Two approaches can be used to gain therapeutic or exogenous control over LTB₄-mediated inflammation. The first, is to inhibit the LTB₄ signal by administration of drugs that act either as LTB₄ membrane receptor antagonists or biosynthesis inhibitors. Indeed, this is a valid approach and many banks of synthetic LTB₄ membrane receptor antagonists and biosynthesis inhibitors have been established. The second approach is to reduce the level of LTB₄ by increasing its metabolism. In vitro, two types of compounds have been shown to modulate LTB₄ metabolism: dietary ω-3 polyunsaturated fatty acids’ and the lipid lowering drug, clofibrate³. The mechanism(s) by which these compounds lower the levels of LTB₄ to exert an anti-inflammatory effect have until recently, been elusive.