Prostaglandin G/H synthase, colloquially known as cyclooxygenase (COX), is a bisfunctional enzyme which catalyses the sequential cyclooxygenation and peroxidation of arachidonic acid to give rise to PGH2, the precursor of a variety of different prostaglandin compounds that have a broad spectrum of biological activity. It is now recognised that there are two forms of this enzyme called COX-1 and COX-2 and the latter, inducible form, has been implicated as the predominant source of eicosanoid generation in inflammatory and possibly proliferative processes. This study will develop a model of COX-2 induction in humans by the intravenous administration of bacterial lipopolysaccharide (LPS). The prostanoid component of the inflammatory response will be assessed by serial measurement of serum and urinary eicosanoid metabolites coincident with the expression of COX-2 ex vivo in monocytes. Finally, the role of an isoprostane, 8 epi PGF 2 alpha, which is formed in a non enzymatic free radical catalysed manner, will be determined in this model of inflammation.
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