%0 Journal Article
%T The Effect of Inflammatory Cytokines in Alcoholic Liver Disease
%A Hideto Kawaratani
%A Tatsuhiro Tsujimoto
%A Akitoshi Douhara
%A Hiroaki Takaya
%A Kei Moriya
%A Tadashi Namisaki
%A Ryuichi Noguchi
%A Hitoshi Yoshiji
%A Masao Fujimoto
%A Hiroshi Fukui
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/495156
%X Alcohol is the most common cause of liver disease in the world. Chronic alcohol consumption leads to hepatocellular injury and liver inflammation. Inflammatory cytokines, such as TNF- and IFN- , induce liver injury in the rat model of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as IL-6, and anti-inflammatory cytokines, such as IL-10, are also associated with ALD. IL-6 improves ALD via activation of the signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via activation of STAT3 in Kupffer cells and the subsequent inhibition of liver inflammation. Alcohol consumption promotes liver inflammation by increasing translocation of gut-derived endotoxins to the portal circulation and activating Kupffer cells through the LPS/Toll-like receptor (TLR) 4 pathways. Oxidative stress and microflora products are also associated with ALD. Interactions between pro- and anti-inflammatory cytokines and other cytokines and chemokines are likely to play important roles in the development of ALD. The present study aims to conduct a systemic review of ALD from the aspect of inflammation. 1. Introduction Alcohol-related liver disease is a major cause of morbidity and mortality worldwide. Chronic alcohol consumption leads to hepatocellular injury, fat accumulation, and liver inflammation and sometimes leads to liver cirrhosis or hepatocellular carcinoma (Figure 1). The pathogenesis of alcoholic liver disease (ALD) is a consequence of chronic alcohol consumption. The clinical syndrome of ALD carries a particularly poor prognosis, such as liver cirrhosis [1] or hepatocellular carcinoma [2]. The pathogenesis of ALD is uncertain, but the relevant factors include metabolism of alcohol to toxic products, oxidative stress, acetaldehyde adducts, abnormal methionine metabolism, malnutrition, the activation of endotoxin, and impaired hepatic regeneration (Figure 2) [3]. Kupffer cells, the resident macrophages in the liver, play the role of an innate immune system; they produce various cytokines and are known to be involved in the pathogenesis of liver diseases [4]. The inflammatory cytokine, tumor necrosis factor-alfa (TNF- ), is involved in acute alcoholic liver injury [5]. Moreover, it is also well known that chronic alcohol consumption increases TNF- production and leads to liver injury [6]. The consumption of alcohol leads to an augmented permeability of the intestinal membrane, which increases the portal concentration of blood
%U http://www.hindawi.com/journals/mi/2013/495156/