Blunted anti-inflammatory response to adenosine in alcoholic cirrhosis

Background/Aims: Adenosine is an endogenous nucleoside that is released und er metabolically unfavourable circumstances such as ischaemia or infection, It exerts potent anti-inflammatory effects by decreasing tumour necrosis f actor release and costimulating interleukin-10 production by human monocyte s, The aim of this study was to assess the cytokine response to adenosine i n whole blood cultures from alcoholic cirrhotic patients. Methods: Whole blood from 17 patients and 17 healthy controls stimulated wi th lipopolysaccharide was cultured in the presence of adenosine at differen t concentrations and, in some experiments, with the adenosine deaminase inh ibitor deoxycoformycin, Peripheral blood mononuclear cell response was comp ared to whole blood, and plasma adenosine deaminase activity,vas measured, Results: Adenosine (100 mu M) significantly inhibited TNF release and incre ased 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 t he absence of autologous plasma, To test the hypothesis that plasma adenosi ne deaminase, which was increased in the patients' plasma, was actually inv olved in this blunted response to adenosine in alcoholic cirrhosis, we perf ormed adenosine dose-response experiments and pharmacologically blocked ade nosine deaminase activity with deoxycoformycin, In both kinds of experiment , adenosine-induced inhibition of TNF release could be restored in alcoholi c cirrhotic patients, Conclusions: These data indicate that increased circulating adenosine deami nase activity blunts the anti-inflammatory properties of adenosine in alcoh olic cirrhotic patients.