Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis.
Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role 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 and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.
Afford
S C
SC
Liver Research Laboratories, University of Birmingham, Edgbaston, U.K.
Fisher
N C
NC
Neil
D A
DA
Fear
J
J
Brun
P
P
Hubscher
S G
SG
Adams
D H
DH
D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006519:Hepatitis, Alcoholic / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008104:Liver Cirrhosis, Alcoholic / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha