Cytokines and fatty liver diseases

Cytokines are considered crucial players in inflammatory-associated disorders throughout the body. Fatty liver diseases such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are commonly characterized by lipid accumulation and in a substantial subset of patients with inflammation in the liver. Amount of inflammation affects long-term outcome of liver disease including evolution of liver fibrosis, cirrhosis and hepatocellular carcinoma. Especially the pro-inflammatory cytokines Interleukin (IL)-1 (α and β) and tumor necrosis factor (TNF) α play a central role in many stages of liver diseases mediating fundamental aspects of those diseases including acute phase protein synthesis, lipid metabolism, cholestasis and degree of fibrosis. These key cytokines released mainly by mononuclear cells affect all liver cell types and orchestrate the production of many other mediators relevant in chronic liver diseases. Inflammatory cytokines also regulate crucially the development of insulin resistance, a key component of NAFLD. Blocking these critical mediators of inflammation by specific antibodies, especially TNFα, has so far not been proven successful in alcoholic steatohepatitis, a cytokine-driven disorder. In summary, inflammatory cytokines are continuously present locally and systemically in patients with advanced fatty liver diseases, mediating and affecting the clinical phenotype and many features of these disorders.