THE ANTIINFLAMMATORY 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 protectiv e 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 co nsequences 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 is chemia and reperfusion are briefly outlined, followed by an extensive discussion of the established and putative anti-inflammatory actions o f adenosine in the inflammatory response to ischemia and reperfusion. It is demonstrated that adenosine interferes with activated neutrophil function, neutrophil-endothelial adhesive interactions, the productio n and release of various inflammatory mediators, the expression of adh esion molecules, and that it activates cellular antioxidant defense sy stems, thus providing protective effects at multiple levels in the pat hogenesis of ischemia and reperfusion. Finally, several potential phar macological strategies to enhance the ''natural defense mechanism'' pr ovided by endogenous adenosine are presented.