INHIBITION OF HUMAN MONOCYTE TNF PRODUCTION BY ADENOSINE RECEPTOR AGONISTS

Adenosine receptor agonists and agents enhancing pericellular concentr ations of adenosine possess antiinflammatory properties. In the presen t study, we found that R-phenylisopropyladenosine (R-PIA), 5'-N-ethylc arboxamido adenosine (NECA), other agonists of adenosine receptors and dipyridamole, an adenosine uptake inhibitor, inhibited tumor necrosis factor (TNF) production by endotoxin-stimulated human monocytes in a concentration-dependent manner with no inhibition of interleukin-6. Th e rank order of agonist potency is characteristic of neither Al nor A2 receptors and suggests the involvement of another receptor subtype. T he effect of R-PIA on TNF was in part abolished by the antagonist 8-su lfophenyltheophylline. In endotoxin-treated rats, R-PIA pretreatment ( 2.5 mg/kg) reduced serum TNF levels by 98 %, with no modification of s erum IL6 levels. TNF inhibition could be an important mechanism by whi ch adenosine analogs exert their antiinflammatory action.