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.
Le Vraux
V
V
Department of Pharmacology, CNRS URA 595, Pavillon G. Roussy, Hôpital Cochin, Paris, France.
Chen
Y L
YL
Masson
I
I
De Sousa
M
M
Giroud
J P
JP
Florentin
I
I
Chauvelot-Moachon
L
L
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