Innate immunity and alcoholic liver disease

UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Publication Date


Document Type



Liver Diseases, Alcoholic; Immunity, Innate




Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, while activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease.

DOI of Published Version



American journal of physiology. Gastrointestinal and liver physiology. 2011 Jan 20. Link to article on publisher's site

Journal/Book/Conference Title

American journal of physiology. Gastrointestinal and liver physiology

Related Resources

Link to Article in PubMed

PubMed ID