Specific alteration of peripheral cytotoxic cell perforin expression in alcoholic patients: A possible role in alcohol-related diseases

Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell-mediated cytotoxicity, in alcoholic patients without cirrhosis. Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral coinfection, other serious medical illness, and immune-related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3(+)CD56(+) T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age- and sex-matched controls. Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 +/- 79/mm(3) versus 271 +/- 192/mm(3); p < 0.03). Perform expression in T CD3(+)/CD56(+) and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 +/- 3% vs. 36 +/- 4% (p < 0.03) and 65 +/- 15% vs. 78 +/- 9% (p = 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups. Conclusions: A decrease in perform expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases.