المؤلفون: Bautista, Abraham P.¹ abauti123@cs.com

المصدر: Alcohol. May2002, Vol. 27 Issue 1, p17-21. 5p.

مصطلحات موضوعية: *ALCOHOLIC liver diseases, *CHEMOKINES, *CYTOKINES, *ALCOHOLISM, *COMPLICATIONS of alcoholism, *ANIMAL experimentation, *COMPARATIVE studies, *HEPATITIS, *IMMUNITY, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *EVALUATION research

مستخلص: Leukocyte infiltration in the liver is one of the most important features of alcoholic liver disease. However, in alcoholic hepatitis, the role of polymorphonuclear neutrophils (PMNs) in liver injury still remains to be fully elucidated. Furthermore, the migration of PMNs and their presence in the liver during alcoholic hepatitis have not been fully investigated. Up-regulation of chemokine secretion and adhesion molecule expression on effector cells (i.e., PMNs) and target cells (i.e., hepatocytes) are important factors in neutrophilic infiltration of the liver. The CXC chemokines—that is, interleukin (IL)-8 (in human beings), cytokine-induced neutrophil chemoattractant (CINC) (in rats), and KC (in mice)—are proneutrophilic agents. They are up-regulated during chronic—that is, several years of—alcohol use in human beings and in up to 30 weeks in experimental models of ethanol intoxication in mice and rats. Up-regulation of these chemokines in the circulation and tissues is also associated with enhanced neutrophilic infiltration in the liver. In the rat, the up-regulation of CXC chemokine production is time dependent. For example, after 16 weeks of feeding, up-regulation of CXC chemokine is observed, whereas after 32 weeks, CC chemokines are enhanced. Concomitantly, selective migration of PMNs and mononuclear cells is observed. In another model, in which both CXC and CC chemokines were enhanced after chronic ethanol use for 12 weeks in mice, neutrophilic and mononuclear/lymphocytic infiltrations were also seen. This model correlates closely with alcoholic hepatitis in human beings, characterized by increased IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 (MIP-1) and profound increases in neutrophils and lymphocytes in the liver. [Copyright &y& Elsevier]

المؤلفون: Bautista, Abraham P

المصدر: Journal of Gastroenterology & Hepatology. Apr2000, Vol. 15 Issue 4, p349-356. 8p. 2 Diagrams, 1 Chart, 1 Graph.

مصطلحات موضوعية: *KUPFFER cells, *CHEMOKINES, *ALCOHOLIC liver diseases, *SECRETION

مستخلص: AbstractChemokines are implicated in the pathogenesis of alcoholic liver disease in humans and in experimental models of alcohol intoxication. The major sources of these chemokines are Kupffer cells which represent more than 80% of tissue macrophages in the body. Kupffer cells are highly responsive to the effects of ethanol, endotoxin and human immunodeficiency virus (HIV)-1 glycoprotein120. These agents, either independently or in combination, may exacerbate the production of chemokines. Chemokines are agents that are highly chemotactic to mononuclear cells and granulocytes. The levels of these chemokines in sera and tissue are elevated in patients with alcoholic hepatitis, alcoholic cirrhosis, diseased livers, viral hepatitis, and in experimental models of chronic alcohol intoxication. Alcohol-induced influx of endotoxin from the gut into the portal circulation is suggested to play an important role in the activation of Kupffer cells which leads to enhanced chemokine release. The up-regulation of chemokines during alcohol consumption is selective. During the early phase of alcoholic liver disease, C-X-C or α- chemokines predominate. This is also associated with neutrophilic infiltration of the liver. In the later stage, up-regulation of C-C or β-chemokine production and migration of mononuclear cells into the liver are observed, and this may lead to liver cirrhosis. Selective up-regulation of chemokine synthesis and release may involve differential modulation of the transcription factors required for chemokine gene expression. Increased cytokine release following alcohol consumption may also regulate chemokine secretion in Kupffer cells via paracrine and autocrine mechanisms and vice versa. In addition, infection with HIV-1 may further compromise the liver to more damage. During HIV-1 infection, a pre-existing liver disease superimposed on chronic alcohol consumption may also exacerbate HIV-1 replication and lymphocytic infiltration in the liver, because of the ability of HIV-1 gp120 to stimulate chemokine production by Kupffer cells and stimulate migration of inflammatory leucocytes in the liver. [ABSTRACT FROM AUTHOR]