Effect of Ethanol on Kupffer Cell Function

Abstract

Kupffer cells are resident macrophages in the liver and are important in both local and systemic immune responses. We evaluated the ability of Kupffer cells in vitro to respond to immune stimulation after both acute exposure to ethanol and after long-term ethanol consumption of ethanol. Triplets of female Wistar rats were fed a liquid diet containing 0, 12, or 36% ethanol isocalorically for 112 days. When killed, the Kupffer cells were isolated by collagenase perfusion and adhered to plastic 24-well plates. They were then stimulated with 10 micrograms/ml lipopolysaccharide for 4.5 hr. Synthesis of procoagulant activity (PCA) and tumor necrosis factor (TNF), expressions of macrophage response to immune stimuli, were measured by a one-step clotting assay and L929 cytotoxicity assay, respectively. Within each of the 10 triplets, PCA and TNF levels were normalized and expressed as a percentage of the zero ethanol isocaloric control rat. The high ethanol group had significantly lower baseline and stimulated PCA and TNF levels than the low ethanol group. For evaluation of the effect of acute exposure to ethanol, Kupffer cells were stimulated with lipopolysaccharide and varying concentrations (0-400 mg/dl) of ethanol. Cells were incubated for 4.5 hr and assayed for PCA and TNF activity. There was dose-dependent inhibition of PCA and TNF, with increasing concentrations of ethanol. These results indicate that whereas exposure to high levels of ethanol depresses Kupffer cell function, lower levels may be immunostimulatory.

Alcohol-induced alterations in serum immunoglobulin E (IgE) levels in human subjects

“…In rats, no serum specific antibodies can be detected after experimental intragastric or intraportal ovalbumin administration, but an increased IgE or IgG1 specific response is observed when Kupffer cells are blocked with gadolinium chloride prior to antigen administration (81,82). Both advanced liver disease and alcohol impair Kupffer cell function (83). In a study of Kupffer cell phagocytic activity (liver radiocolloid uptake), serum IgE levels and skin prick test reactivity to a battery of food allergens in a group of 52 cirrhotics (27 of them of alcoholic origin), we observed that IgE elevation was restricted to alcoholic cirrhotics, and unrelated to either liver phagocytic function or skin test reactivity to food allergens (32).…”