CHEMOKINE LEVELS IN HUMAN LIVER HOMOGENATES - ASSOCIATIONS BETWEEN GRO ALPHA AND HISTOPATHOLOGICAL EVIDENCE OF ALCOHOLIC HEPATITIS

Alcoholic hepatitis is characterized by parenchymal neutrophil infiltr ation. Hepatic synthesis of the neutrophil chemokine interleukin-8 (IL -8) is highly elevated in alcoholic hepatitis and levels correlate wit h the degree of neutrophil infiltration. The aim of this study was to further determine the spectrum of synthesis of chemokines in liver tis sue from patients with alcoholic liver disease and a range of disease control subjects. Subjects were composed of 24 patients with alcoholic liver disease of whom 15 had histopathological evidence of alcoholic hepatitis (10 cirrhotic) and 9 no evidence of alcoholic hepatitis (5 c irrhotic); other controls included; normal liver (n = 6), viral hepati tis (n = 16), primary biliary cirrhosis (n = 5), acute liver failure ( n = 4), and miscellaneous Liver disease (n = 13), Levels of the C-X-C neutrophil chemokine GRO alpha and the mononuclear cell C-C chemokines : macrophage inflammatory protein 1 alpha, macrophage chemotactic prot ein 1 and RANTES, were determined by ELISA in liver homogenates. Level s of the neutrophil chemokine GRO alpha were specifically elevated (me an 46 pg/mg, compared with normal liver 11 pg/mg) in patients with alc oholic hepatitis. GRO alpha levels correlated with IL-8 levels and wer e higher in patients with alcoholic liver disease and parenchymal neut rophil infiltration. Hepatic RANTES was elevated in diseased liver, wi th the highest levels found in viral hepatitis (mean 117 pg/mg, compar ed with 24 pg/mg in normal liver). No significant changes in hepatic l evels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) or macr ophage chemotactic protein 1 (MCP-1) were found. These data provide fu rther supportive evidence that parenchymal neutrophil infiltration in alcoholic hepatitis may be determined by selective upregulation of C-X -C chemokine synthesis.