It is also critical to take into consideration that the effects of ethanol on immune function in vivo could involve the actions of its primary metabolite, acetaldehyde. Therefore, more studies looking at the effects of ethanol metabolites in vivo are needed. Acetaldehyde has also been shown to affect NFκB-induced cytokine production in various liver cells. In the presence of acetaldehyde, Kupffer cells, the specialized macrophages in the liver, treated with LPS show decreased NFκB activation (Jokelainen, Thomas et al. 1998), while hepatic stellate cells, the major producers of collagen that accumulate during hepatic fibrosis, show enhanced NFκB activation (Novitskiy, Ravi et al. 2005). Finally, acetaldehyde disrupts intestinal epithelial barrier function and increases paracellular permeability which plays a crucial role in the pathogenesis of alcoholic liver disease by a tyrosine kinase-dependent mechanism (Sheth, Seth et al. 2004).
