The role of leukotrienes in the pathophysiology of inflammatory disorders: is there a case for revisiting leukotrienes as therapeutic targets?

Abstract

Leukotrienes (LTs), a family of lipid mediators, play a key role in the pathogenesis of inflammation. They are synthesized in the leucocytes from arachidonic acid (AA) via the actions of 5-lipoxygenase (5-LO). LTs are classified into two classes: LTB(4) and cysteinyl LTs (CysLTs). LTB(4) is one of the most potent chemoattractant mediators of inflammation. It exerts its actions through a seven transmembrane-spaning G protein receptors, LTB4 R-1 and LTB4 R-2. CysLTs (LTC(4), LTD(4), and LTE(4)) are potent bronchoconstrictors that play an important role in asthma. They induce their actions through G protein coupled receptors, CysLT R-1 and CysLT R-2. LTs are involved in the pathogenesis of inflammatory disorders specially asthma, rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Therefore, LTs modifiers, LTs inhibitors or antagonists, represent important therapeutic advance in the management of inflammatory diseases. Zileuton, zafirlukast and montelukast are LTs modifiers that are approved to use for the treatment of inflammatory disorders.