PMID: 11329499May 1, 2001Paper

Pro- and anti-inflammatory gene expression in the murine small intestine and liver after chronic exposure to alcohol

Alcoholism, Clinical and Experimental Research
S FlemingE S Metcalf

Abstract

Endotoxin has been proposed to play a primary role in ALD, by initiating an inflammatory cascade within the liver. Although the source of these cytokines has been presumed to be circulating monocytes or tissue macrophages, ethanol-induced, nonhepatic sources of soluble mediators recently have been identified. One potential, but not clearly defined, extrahepatic source of cytokines in ALD is the intestine. In the current study, we hypothesized that alcohol would alter cytokine expression within the small intestine of mice exposed to ethanol and that LPS would alter levels of cytokine expression even more dramatically. Mice were fed a modified Lieber-DeCarli liquid ethanol or control diet for up to 14 days prior to injecting either saline or LPS. Plasma alanine aminotransferase (ALT) and cytokine levels, histology, and RT-PCR of pro- and anti-inflammatory cytokine gene expression were determined from distal ileum and liver samples. Translocation of intestinal bacterial flora also was assessed. Ethanol exposure upregulated basal gene expression of IL-1 beta, TNF-alpha, IL-6, and iNOS in the distal ileum, but similar effects of ethanol on the liver were not observed. In contrast, LPS challenge of ethanol-exposed mice increased inte...Continue Reading

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