Eicosanoid Synthesis and Respiratory Distress Syndrome in Intensive Medicine

Abstract

Eicosanoids are signaling molecules made by oxidation of 20 carbon fatty acids. They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. Eicosanoids control both proinflammatory and anti-inflammatory effectors that are particularly relevant for inflammation. The networks of controls that depend upon eicosanoids are among the most complex in the human body. Lipid mediators are synthesized via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways with fatty acids such as arachidonic acid used as substrate. These mediators include prostaglandins, thromboxanes, leukotrienes, lipoxins, and hydroxyl and epoxy fatty acids – all grouped as eicosanoids – and platelet-activating factor, acting as intercellular signaling molecules. They have an impact on the secretion of immunoregulatory cytokines, on secondary mediators like reactive oxygen species or proteases, and on autocrine eicosanoid regulation loops. Numerous experimental studies suggest that the generation of arachidonate metabolites can play a role in the development of ALI/RDS. In normal conditions, arachidonate is bound to the phospholipids of cell membranes. Following injury and in response to various mediators, free arachidonic acids are released from membrane phospholipids by the action of phospholipases. This arachidonic acid can serve as a substrate for the production of prostaglandins and thromboxanes through a cyclooxygenase enzyme and as a substrate for the production of several hydroxyl fatty acids and leukotrienes through the action of lipoxygenase enzymes. The lung is an important organ in the arachidonate cascade since it possesses the enzymatic capacity to synthesize all the arachidonate derivatives and also responsible in large part for selective catabolism of circulating eicosanoids. The use of diets high in w-3 fatty acids is a means to decrease levels of arachidonic acid in cells, thereby reducing the production of proinflammatory eicosanoids. Clinical investigation with enteral diets enriched in EPA/GLA and antioxidants shows beneficial effect in patients with ALI/ARDS.