CIRCULATING AND TISSUE-LEVELS OF THE NEUTROPHIL CHEMOTAXIN INTERLEUKIN-8 ARE ELEVATED IN SEVERE ACUTE ALCOHOLIC HEPATITIS, AND TISSUE-LEVELS CORRELATE WITH NEUTROPHIL INFILTRATION

Acute alcoholic hepatitis is characterized by a unique degree of liver neutrophil infiltration, often accompanied by marked peripheral neutrophilia in the absence of demonstrable bacterial or fungal infection. In this study we assayed plasma and tissue levels of a potent neutrophil activator and chemotaxin, interleukin-8, in patients with a spectrum of alcoholic liver diseases and in normal and diseased control subjects. Levels of circulating interleukin-8 were undetectable in normal subjects but highly elevated in patients with alcoholic hepatitis, particularly in those who died (geometric mean = 600 ng/L; confidence interval = 323 to 1,120 vs. geometric mean = 184 ng/L; confidence interval = 114 to 309 in survivors). Levels correlated with biochemical indicators of severe disease (bilirubin: R = 0.38; international prothrombin ratio: R = 0.28; white blood cell count: R = 0.35; creatinine: R = 0.34) and with tumor necrosis factor-a (R = 0.43) and soluble tumor necrosis factor receptors (p55; R = 0.59). In contrast, moderate elevations in the levels of circulating interleukin-8 were seen in alcoholic cirrhosis (geometric mean = 93 ng/L; confidence interval = 40 to 213) and in alcoholic patients undergoing alcohol withdrawal (geometric mean = 137 ng/L; confidence interval = 72 to 259). Levels in nonalcoholic inflammatory liver disease were comparatively low (geometric mean = 17 ng/L; confidence interval = 10 to 29). In liver tissue from patients with alcoholic liver disease, local levels of interleukin-8 correlated with degree of neutrophil infiltration (R = 0.71; n = 16), and levels were much higher in alcoholic hepatitis (987 pg/mg; confidence interval = 351 to 1623) than in other alcoholic liver diseases (103 pg/mg; confidence interval = 0 to 220), normal liver (20 pg/mg; confidence interval = 0 to 61) and nonalcoholic liver disease (219 pg/mg; confidence interval = 142 to 295). Immunohistochemical study confirmed widespread parenchymal expression of interleukin-8 in alcoholic hepatitis patients with the most severe degrees of neutrophil infiltration. Interleukin-8 may play a role in mediating the infiltration of neutrophils and the effects of neutrophil activation so characteristic of acute alcoholic hepatitis.