LIPID MEDIATORS IN INFLAMMATORY DISORDERS

During the past few decades, intensive collaborative research in the f ields of chronic and acute inflammatory disorders has resulted in a be tter understanding of the pathophysiology and diagnosis of these disea ses. Modern therapeutic approaches are still not satisfactory and shoc k, sepsis and multiple organ failure remain the great challenge in int ensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also repres ents an unresolved problem. Many factors contribute to the complex cou rse of inflammatory reactions. Microbiological, immunological and toxi c agents can initiate the inflammatory response by activating a variet y of humoral and cellular mediators. In the early phase of inflammatio n, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arac hidonic acid (AA), the mother substance of the pro-inflammatory eicosa noids, is released from membrane phospholipids in the course of inflam matory activation and is metabolised to prostaglandins and leukotriene s. Various strategies have been evaluated to control the excessive pro duction of lipid mediators on different levels of biochemical pathways , such as inhibition of phospholipase A(2), the trigger enzyme for rel ease of AA, blockade of cyclo-oxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating fa ctor and leukotrienes. Some of these agents exert protective effects i n different inflammatory disorders such as septic organ failure, rheum atoid arthritis or asthma, whereas others fail to do so. Encouraging r esults have been obtained by dietary supplementation with long chain o mega-3 fatty acids like eicosapentaenoic acid (EPA). In states of infl ammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivativ es.