New insights into the anti-inflammatory actions of aspirin-induction of nitric oxide through the generation of epi-lipoxins.
Aspirin has always remained an enigmatic drug. Not only does it present with new benefits for treating an ever-expanding list of apparently unrelated diseases at an astounding rate but also because aspirin enhances our understanding of the nature of these diseases process. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins, fatty acid metabolites that modulate host defense. However, in addition to inhibiting cyclooxygenase activity aspirin can also inhibit pro-inflammatory signaling pathways, gene expression and other factors distinct from eicosanoid biosynthesis that drive inflammation as well as enhance the synthesis of endogenous protective anti-inflammatory factors. Its true mechanism of action in anti-inflammation remains unclear. Here the data from a series of recent experiments proposing that one of aspirin's predominant roles in inflammation is the induction of nitric oxide, which potently inhibits leukocyte/endothelium interaction during acute inflammation, will be discussed. It will be argued that this nitric oxide-inducing effects are exclusive to aspirin due to its unique ability, among the family of traditional anti-inflammatory drugs, to acetylate the active site of inducible cyclooxygenase and generate a family of lipid mediators called the epi-lipoxins that are increasingly being shown to have profound roles in a range of host defense responses.
Gilroy
Derek W
DW
BHF Laboratories, Division of Medicine, Centre for Clinical Pharmacology and Therapeutics, University College London, London WC1E 6JJ, UK. d.gilroy@ucl.ac.uk
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D044045:Lipoxins / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D018836:Inflammation Mediators; D044045:Lipoxins; D009569:Nitric Oxide; D001241:Aspirin