Inhibition of LPS-induced TNF alpha production in human monocytes by adenosine (A2) receptor selective agonists.

We examined the effects of adenosine A1 and A2 receptor agonists on LPS-stimulated TNF alpha production by human monocytes isolated from peripheral blood. We have demonstrated that CGS-21680, a highly selective A2 agonist inhibited production of TNF alpha at the protein level by 75% whereas the A1 selective agonist N6 reduced TNF alpha production by only 25%. The action of CGS-21680 was mediated via the A2 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 A2 and A1 receptors, respectively. Thus intervention with A2-selective agonists or compounds that can elevate endogenously released adenosine may be beneficial in TNF alpha-mediated diseases.