Blunted anti-inflammatory response to adenosine in alcoholic cirrhosis.
OBJECTIVE
Adenosine is an endogenous nucleoside that is released under metabolically unfavourable circumstances such as ischaemia or infection. It exerts potent anti-inflammatory effects by decreasing tumour necrosis factor release and costimulating interleukin-10 production by human monocytes. The aim of this study was to assess the cytokine response to adenosine in whole blood cultures from alcoholic cirrhotic patients.


METHODS
Whole blood from 17 patients and 17 healthy controls stimulated with lipopolysaccharide was cultured in the presence of adenosine at different concentrations and, in some experiments, with the adenosine deaminase inhibitor deoxycoformycin. Peripheral blood mononuclear cell response was compared to whole blood, and plasma adenosine deaminase activity was measured.


RESULTS
Adenosine (100 microM) significantly inhibited TNF release and increased IL-10 production in whole blood cultures from controls stimulated with lipopolysaccharide, but not from cirrhotic patients. However, the response to adenosine was restored in peripheral mononuclear cells of patients in the absence of autologous plasma. To test the hypothesis that plasma adenosine deaminase, which was increased in the patients' plasma, was actually involved in this blunted response to adenosine in alcoholic cirrhosis, we performed adenosine dose-response experiments and pharmacologically blocked adenosine deaminase activity with deoxycoformycin. In both kinds of experiment, adenosine-induced inhibition of TNF release could be restored in alcoholic cirrhotic patients.


CONCLUSIONS
These data indicate that increased circulating adenosine deaminase activity blunts the anti-inflammatory properties of adenosine in alcoholic cirrhotic patients.
Le Moine
O
O
Department of Gastroenterology, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium. olemoine@ulb.ac.be
Quertinmont
E
E
Gulbis
B
B
Devière
J
J
D000241:Adenosine / Q000627:therapeutic use*; D058892:Adenosine Deaminase Inhibitors; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000494:pharmacology; D013268:Stimulation, Chemical
D058892:Adenosine Deaminase Inhibitors; D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D015649:Pentostatin; D000241:Adenosine