Leukotrienes: lipid bioeffectors of inflammatory reactions

The leukotrienes arise from oxidative metabolism of arachidonic acid through the action of the 5-lipoxygenase enzyme, leading to the unstable allylic epoxide leukotriene A4. This intermediate represents the substrate for two different specific enzymes, namely leukotriene A4-hydrolase and leukotriene C4-synthase, generating LTB4 and cysteinyl leukotrienes, respectively. The name "leukotriene" is referring to the cellular source (leukocytes are one of the major sources) as well as the conjugated triene that characterizes their structure. LTC4 and LTD4 are potent contracting agents of smooth muscle in airways and blood vessels; in addition, they induce mucus secretion and promote plasmatic exudation with direct action on endothelial cells. On the other side, LTB4 is known as a potent chemokinetic and chemotactic agent. A number of evidences reported in the literature underline the potential role of leukotrienes in the inflammatory responses that characterize asthma and other pathological conditions. These potent lipid bioeffectors are synthesized during the course of inflammatory reactions and their pharmacological modulation is able to significantly attenuate the clinical manifestations associated with different inflammatory pathologies.