Arachidonic acid endothelial cell damage

TNF-a is considered the primary mediator of sepsis, and concentrations are elevated early in the inflammatory response during sepsis, and there is a correlation with severity of sepsis. TNF-a release leads to activation of other cytokines associated with cellular damage and it stimulates release of arachidonic acid metabolites that contribute to endothelial cell damage. IL-6 is a more consistent predictor of sepsis as it remains elevated for longer periods of time than does TNF-a. 

W., 1981 Prostacyclin production in rabbit arteries in situ inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin. Prostaglandins 21, 655-666. 

Enhanced production of vasoconstrictor factors via eicosanoid and/or free radical-related mechanisms has been observed in several cardiovascular disease states. In addition to the well-established role of free radicals in promoting the oxidation of low density lipoprotein cholesterol (LDL-C), changes in free radical status may modify endogenous eicosanoid profiles and/or produce nonenzymatic lipid peroxidation products of the arachidonic acid (AA) cascade such as lipid hydroperoxides and isoprostanes, which have been shown to possess potent vasoactive properties (3). Furthermore, an excess of free radicals may interact with the vascular endothelial cell nitric oxide (NO) to produce highly reactive peroxynitrite radicals, resulting in tissue damage and vasoconstriction (4—6) (Fig. 2). 

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