Anti-inflammatory effects of adenosine kinase inhibitors in acute and chronic inflammation

Adenosine (Ado) exhibits a variety of anti-inflammatory activities, including inhibition of neutrophil oxygen radical production, adhesion to vascular endothelium and macrophage TNF-alpha gene expression. The therapeutic uses of Ado and its analogues, however, are limited by severe side effects like hypotension and bradycardia. Therefore, adenosine regulating agents with site and event specificity have been developed to enhance endogenous adenosine production. Adenosine kinase inhibitors were especially active anti-inflammatory agents and demonstrated efficacy in several models, including carrageenan paw edema, carrageenan air pouch, and adjuvant arthritis in rats. These studies suggest that adenosine kinase inhibitors have potential utility in diseases like rheumatoid arthritis. (C) 1997 Wiley-Liss, Inc.