Effect of acute alcohol administration on TNF-alpha binding to neutrophils and isolated liver plasma membranes.

Abstract

The mechanisms underlying the effects of alcohol (ethanol, ETOH) on host defense are poorly understood. ETOH modulation of the cytokine regulatory network is one possible way by which ETOH could alter nonspecific immune function. In this study we examined the ability of acute alcohol intoxication to alter lipopolysaccharide (LPS)-induced changes in tumor necrosis factor (TNF)-alpha binding to neutrophils and isolated liver plasma membranes. Rats were injected intravenously with a primed constant infusion of ETOH for 7 hr to maintain blood ETOH concentration at approximately 35 mM. Four hours after the start of ETOH infusion, the animals received intravenously either sterile saline or LPS (100 micrograms/100 g body weight) and were sacrificed at the end of ETOH infusion. Blood neutrophils and liver plasma membranes were isolated, and TNF-alpha binding characteristics determined using recombinant human [125I]TNF-alpha. ETOH treatment alone induced a significant decrease (51%) of neutrophil Bmax for TNF-alpha, without affecting the cytokine binding to plasma membranes. LPS, with or without ETOH, significantly decreased (61%) neutrophil Bmax for TNF-alpha and increased (115%) its binding to liver plasma membranes. The KD values of binding to either neutrophils or liver plasma membranes were not altered by ETOH or LPS treatment of animals. By decreasing the cytokine binding to neutrophils, ETOH may impair the control exerted by TNF-alpha on cell function, thus damaging host defense.