REVIEW: Leukotrienes: Lipid Bioeffectors of Inflammatory Reactions

A. Sala^*, S. Zarini, and M. Bolla

Center for Cardiopulmonary Pharmacology, University of Milan, Via Balzaretti 9, 20133 Milan, Italy; fax: (39) 2-29404961; E-mail: angelo.sala@unimi.it

^* To whom correspondence should be addressed.

Received July 22, 1997

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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 characterizes 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.

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KEY WORDS: 5-lipoxygenase, leukotrienes, chemotaxis, bronchoconstriction, leukocytes, LTC₄-synthase

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