Lipid mediators in inflammatory disorders

• Published in: Drugs (New York, N.Y.) Vol. 55; no. 4; pp. 487 - 496
• Main Authors: HELLER, A, KOCH, T, SCHMECK, J, VAN ACKERN, K
• Format: Journal Article
• Language: English
• Published: Auckland Adis International 01.04.1998; Springer International Publishing
• Subjects: Animals; Arachidonic Acid - metabolism; Biological and medical sciences; Cyclooxygenase Inhibitors - therapeutic use; Fatty Acids, Omega-3 - therapeutic use; Fundamental and applied biological sciences. Psychology; Humans; Inflammation; Inflammation - metabolism; Inflammation - therapy; Inflammation Mediators - metabolism; Leading; Leukotriene Antagonists; Lipid Metabolism; Lipoxygenase Inhibitors - therapeutic use; Molecular and cellular biology; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Phospholipids - metabolism; Platelet Activating Factor - antagonists & inhibitors; Prostaglandins - metabolism; Prostaglandin-endoperoxide synthase; Lipids; Esterases; Supplemented diet; Review; Arachidonic acid; n-3 fatty acid; Antagonist; Supplementation; Pathophysiology; Prostaglandin; Enzyme; Antiinflammatory agent; Polyunsaturated fatty acid; Enzyme inhibitor; Inflammation; Fatty acids; Phospholipase A; Platelet activating factor; Carboxylic ester hydrolases; Non steroidal antiinflammatory agent; Immunomodulator; Leukotriene; Hydrolases; Oxidoreductases; Eicosapentaenoic acid
• ISSN: 0012-6667; 1179-1950
• DOI: 10.2165/00003495-199855040-00001

During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.