Inhibition of human monocyte TNF production by adenosine receptor agonists.
Adenosine receptor agonists and agents enhancing pericellular concentrations of adenosine possess antiinflammatory properties. In the present study, we found that R-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamido 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. The rank order of agonist potency is characteristic of neither A1 nor A2 receptors and suggests the involvement of another receptor subtype. The effect of R-PIA on TNF was in part abolished by the antagonist 8-sulfophenyltheophylline. In endotoxin-treated rats, R-PIA pretreatment (2.5 mg/kg) reduced serum TNF levels by 98%, with no modification of serum IL6 levels. TNF inhibition could be an important mechanism by which adenosine analogs exert their antiinflammatory action.
Department of Pharmacology, CNRS URA 595, Pavillon G. Roussy, Hôpital Cochin, Paris, France.
V
V
Le Vraux
Y L
YL
Chen
I
I
Masson
M
M
De Sousa
J P
JP
Giroud
I
I
Florentin
L
L
Chauvelot-Moachon
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001681:Biological Assay; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007739:L Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004731:Endotoxins; D008070:Lipopolysaccharides; D011983:Receptors, Purinergic; D014409:Tumor Necrosis Factor-alpha; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C024311:N-cyclopropyl adenosine-5'-carboxamide; D004176:Dipyridamole; D003907:Dexamethasone; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine