The anti-inflammatory potential of adenosine in ischemia-reperfusion injury: established and putative beneficial actions of a retaliatory metabolite.
The endogenous metabolite adenosine has been recognized as a protective agent in the setting of ischemia-reperfusion. Because the formation of adenosine during ischemia is closely linked to ATP catabolism, and its actions antagonize the deleterious metabolic and cardiovascular consequences of ischemia, it has been named a "retaliatory" metabolite. During recent years, however, the insight into its diverse scope of anti-inflammatory actions has increased considerably. In this review, the beneficial metabolic and cardiovascular actions of adenosine in ischemia and reperfusion are briefly outlined, followed by an extensive discussion of the established and putative anti-inflammatory actions of adenosine in the inflammatory response to ischemia and reperfusion. It is demonstrated that adenosine interferes with activated neutrophil function, neutrophil-endothelial adhesive interactions, the production and release of various inflammatory mediators, the expression of adhesion molecules, and that it activates cellular antioxidant defense systems, thus providing protective effects at multiple levels in the pathogenesis of ischemia and reperfusion. Finally, several potential pharmacological strategies to enhance the "natural defense mechanism" provided by endogenous adenosine are presented.
Bouma
M G
MG
Department of Surgery, Maastricht University, The Netherlands.
van den Wildenberg
F A
FA
Buurman
W A
WA
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D058892:Adenosine Deaminase Inhibitors; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019194:Ischemic Preconditioning; D009705:Nucleosides / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D009705:Nucleosides; D018047:Receptors, Purinergic P1; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D000255:Adenosine Triphosphate; D000248:Adenosine Kinase; D000241:Adenosine