Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

BACKGROUND: Long-term excess alcohol intake predisposes to infectious diseases. The hepatic acute phase response is a component of the innate immune system and is part of the first line of defense against invading pathogens, which may be compromised by alcohol. We aimed to investigate whether an induced acute phase response is impaired in long-term ethanol-fed rats.METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins.RESULTS: Ethanol-fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (PCONCLUSIONS: Long-term ethanol exposure in rats reduces the spontaneous hepatic mRNA expression of alpha-2-macroglobulin and markedly impairs the hepatic acute phase response to endotoxin, despite higher pro-inflammatory cytokine release. The same phenomenon may contribute to the increased susceptibility to infections observed in humans with long-term excess alcohol intake. This article is protected by copyright. All rights reserved.