DISTINCT PATTERNS OF CHEMOKINE EXPRESSION ARE ASSOCIATED WITH LEUKOCYTE RECRUITMENT IN ALCOHOLIC HEPATITIS AND ALCOHOLIC CIRRHOSIS

Alcoholic liver disease is associated with three histologically distin ct processes: steatosis (parenchymal fat accumulation), alcoholic hepa titis (characterized by parenchymal infiltration by neutrophil polymor phs), and alcoholic cirrhosis (in which chronic inflammation and fibro sis dominate). Chemokines are cytokines that promote subset-specific l eukoycte recruitment to tissues and could therefore play a crucial rol e in determining which Leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease an d, moreover, that distinct patterns of chemokine expression are associ ated with the different inflammatory responses to alcohol. Interleukin -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage infl ammatory protein-1 alpha (MLP-1 alpha), and MIP-1 beta were all detect ed in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflamma tory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoid al cells, leukocytes, and fibroblasts in areas of parenchymal inflamma tion, but hepatocytes, despite staining strongly for chemokine protein , were negative. In alcoholic cirrhosis, chemokine mRNA was detected i n portal tract endothelium, leukocytes, and fibroblasts. Thus, alcohol ic hepatitis and alcoholic cirrhosis are associated with distinct patt erns of chemokine expression that are likely to be important factors i n determining whether a patient develops acute parenchymal inflammatio n and alcoholic hepatitis, or chronic septal inflammation and alcoholi c cirrhosis. (C) 1998 John Wiley & Sons, Ltd.