LEUKOTRIENES - LIPID BIOEFFECTORS OF INFLAMMATORY REACTIONS

The leukotrienes arise from oxidative metabolism of arachidonic acid t hrough the action of the 5-lipoxygenase enzyme, leading to the unstabl e allylic epoxide leukotriene A(4). This intermediate represents the s ubstrate for two different specific enzymes, namely leukotriene A(4)-h ydrolase and leukotriene C-4-synthase, generating LTB4 and cysteinyl l eukotrienes, respectively. The name ''leukotriene'' is referring to th e cellular source (leukocytes are one of the major sources) as well as the conjugated triene that characterizes their structure. LTC4 and LT D4 are potent contracting agents of smooth muscle in airways and blood vessels; in addition, they induce mucus secretion and promote plasmat ic exudation with direct action on endothelial cells, On the other sid e, LTB4 is known as a potent chemokinetic and chemotactic agent, A num ber of evidences reported in the literature underline the potential ro le of leukotrienes in the inflammatory responses that characterize ast hma 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 cli nical manifestations associated with different inflammatory pathologie s.