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Altered hepatic lymphocyte subpopulations in obesity‐related murine fatty livers: Potential mechanism for sensitization to liver damage
Author(s) -
GuebreXabier Mimi,
Yang ShiQi,
Lin Hui Zhi,
Schwenk Robert,
Krzych Ursula,
Diehl Anna Mae
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510310313
Subject(s) - fatty liver , endocrinology , medicine , cytokine , biology , immunology , peripheral blood mononuclear cell , lymphocyte , interleukin 10 , disease , biochemistry , in vitro
Although obesity‐related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure. The purpose of this study was to determine if immunologic priming might be involved by determining if fatty livers resemble normal livers that have been sensitized to endotoxin damage by Propionibacterium acnes infection. The latter induces interleukin (IL)‐12 and ‐18, causing a selective reduction of CD4+NK T cells, diminished IL‐4 production, deficient production of T‐helper type 2 (Th‐2) cytokines ( e.g. , IL‐10), and excessive production of Th‐1 cytokines ( e.g. , interferon gamma [IFN‐γ]). Liver and spleen lymphocyte populations and hepatic cytokine production were compared in genetically obese, ob/ob mice (a model for obesity‐related fatty liver) and lean mice. Obese mice have a selective reduction of hepatic CD4+NK T cells. Serum IL‐18 is also increased basally, and the hepatic mRNA levels of IL‐18 and ‐12 are greater after endotoxin challenge. Thus, up‐regulation of IL‐18 and IL‐12 in fatty livers may reduce hepatic CD4+NK T cells. In addition, mononuclear cells from fatty livers have decreased expression of the adhesion molecule, leukocyte factor antigen‐1 (LFA‐1), which is necessary for the hepatic accumulation of CD4+NK T cells. Consistent with reduced numbers of hepatic CD4+NK T cells, mononuclear cells from fatty livers produce less IL‐4. Furthermore, after endotoxin treatment, hepatic induction of IL‐10 is inhibited, while that of IFN‐γ is enhanced. Thus, fatty livers have inherent immunologic alterations that may predispose them to damage from endotoxin and other insults that induce a proinflammatory cytokine response.

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