Leukotrienes and Inflammation –A Review

Abstract

Leukotrienes, together with the prostaglandins and other related compounds, are derived from 20 carbon
(eicosa) fatty acids that contain double bonds (enoic). Hence this group of substances is called the
eicosanoids. The name leukotriene derives from the original discovery of these substances in white blood
cells (polymorphonuclear leucocytes) and the fact that they all have in common 4 double bonds (hence the
4 subscript), 3 of which are in a conjugated triene structure. Leukotrienes do not exist preformed in cells.
They are formed from the breakdown of arachidonic acid, a polyunsaturated 20 carbon fatty acid. In its
esterified form, arachidonic acid is bound to the phospholipids of the cell membranes. Both immunological
and non-immunological stimuli can release arachidonic acid from membrane phospholipids by activating
phospholipase A2. The glucocorticosteroid drugs can inhibit phospholipase A2 and thereby decrease the
production of all the leukotrienes and hence leukotriene-mediated responses. Generally, inflammation leads
to vasodilation, vascular hyperpermeability, increased blood flow and recruitment of leukocytes to inflamed
sites. These events cause enhanced production of cytokines, chemokines, chemical mediators and lipid
mediators such as LTs and prostaglandins. Acute inflammation occurs over a short time (seconds, minutes
and hours). In contrast, chronic inflammation is a long-lasting inflammatory and immune response that
occurs over months to years and results in diverse diseases including asthma, allergies, atherosclerosis,
arthritis, obesity, cancer and other age-related diseases such as AMD. In this review article we aimed to
highlight the evidence that implicates LTs in physiological function and also in disease processes.