Elevated Circulating and Tissue IL-8 in Alcoholic Hepatitis

Acute alcoholic hepatitis is characterised by a unique degree of liver neutrophil infiltration, often accompanied by marked peripheral neutrophilia. We examined plasma (n = 164) and tissue (n = 50) levels of the neutrophil activator and chemotaxin, interleukin8, in patients with a spectrum of alcoholic liver disease, and in normal and disease control subjects. Levels of circulating IL-8 were undetectable in normals but highly elevated in patients with alcoholic hepatitis particularly in those who died (gM 600 ng/l, Cl 323-1120 v 184 ng/1, Cl 114-309 in survivors). Levels correlated with biochemical indicators of severe disease (bilirubin R = 0.38, INR R = 0.28, WCC R = 0.35, creatinine R = 0.34), and with TNFα (R = 0.43) and soluble TNF receptors (p55 R = 0.59). In contrast moderate elevations in the level of circulating IL-8 were seen in alcoholic cirrhosis (gM 93 ng/1, Cl 40-213) and in alcoholics undergoing alcohol withdrawal (gM 137 ng/l, Cl 72-259). Levels in non-alcohol related inflammatory liver disease were comparatively low (gM 17 ng/l, Cl 10-29). In liver tissue from patients with alcoholic liver disease, local levels of IL-8 correlated with the degree of neutrophil infiltration (R = 0.71, n = 15) and levels were much higher in alcoholic hepatitis (987 pg/mg, Cl 351-1623) compared with other alcoholic liver disease (103 pg/mg, Cl 0-220), normal liver (20 pg/mg, Cl 0-61) and non-alcohol related liver disease (219 pg/mg, Cl 142-295). Synthesis of IL-8 within the liver may play a role in the pathogenesis of alcoholic liver disease.