THE PPAR-ALPHA-LEUKOTRIENE B-4 PATHWAY TO INFLAMMATION CONTROL

Inflammation is a local immune response to 'foreign' molecules, infect ion and injury. Leukotriene B-4, a potent chemotactic agent that initi ates, coordinates, sustains and amplifies the inflammatory response, i s shown to be an activating ligand for the transcription factor PPAR a lpha. Because PPAR alpha regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mech anism is proposed that controls the duration of an inflammatory respon se and the clearance of leukotriene B-4 in the liver. Thus PPAR alpha offers a new route to the development of anti- or pro-inflammatory rea gents.