Relation of tumor necrosis factor (TNF) gene polymorphisms with serum concentrations and in vitro production of TNF-alpha and interleukin-8 in heavy drinkers.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) play a role in the pathogenesis of alcoholic hepatitis. The aim of the current study was to investigate the possible relation of TNF gene polymorphisms with TNF-alpha and IL-8 synthesis in heavy drinkers. Nineteen heavy drinkers and 14 healthy control subjects were included in the study. Investigations included (a) polymorphisms in the TNF promoter region at positions -238 (G-->A), -308 (G-->A), -857 (C-->T), and -863 (C-->A), as well as a biallelic Ncol restriction fragment length polymorphism in the first intron of the close TNF-beta gene; (b) serum TNF-alpha and IL-8 concentrations; and (c) TNF-alpha and IL-8 production by phytohemagglutinin A-stimulated peripheral blood mononuclear cells. In comparison with findings for control subjects, heavy drinkers showed higher TNF-alpha production, higher IL-8 production, and higher serum IL-8 concentrations. Increased serum TNF-alpha concentrations were specifically found in heavy drinkers with the -857 (C-->T) substitution (CT heterozygotes), therefore indicating an interaction between alcohol consumption and that polymorphism on serum TNF-alpha concentrations.