INHIBITION OF LPS-INDUCED TNF-ALPHA PRODUCTION IN HUMAN MONOCYTES BY ADENOSINE (A(2)) RECEPTOR-SELECTIVE AGONISTS

We examined the effects of adenosine A(1) and A(2) receptor agonists on LPS-stimulated TNF alpha production by human monocytes isolated from peripheral blood. We have demonstrated that CGS-21680, a highly selective A(2) agonist inhibited production of TNF alpha at the protein level by 75% whereas the A(1) selective agonist N-6 reduced TNF alpha production by only 25%. The action of CGS-21680 was mediated via the A(2) receptors since its effect on TNF production was blocked by 3,7-dimethyl-1-propargylxanthine (DMPX) but not by xanthine amine cogener (XAC), antagonists selective for the A(2) and A(1) receptors, respectively. Thus intervention with A(2)-selective agonists or compounds that can elevate endogenously released adenosine may be beneficial in TNF alpha-mediated diseases.