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Prevention of lethal acute hepatic failure by antimacrophage migration inhibitory factor antibody in mice treated with bacille calmette‐guerin and lipopolysaccharide

Kobayashi, Seiji ; Nishihira, Jun ; Watanabe, Satoshi ; Todo, Satoru

Hepatology (Baltimore, Md.), 1999-06, Vol.29 (6), p.1752-1759 [Periódico revisado por pares]

Philadelphia, PA: W.B. Saunders

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Título:
Prevention of lethal acute hepatic failure by antimacrophage migration inhibitory factor antibody in mice treated with bacille calmette‐guerin and lipopolysaccharide
Autor: Kobayashi, Seiji ; Nishihira, Jun ; Watanabe, Satoshi ; Todo, Satoru
Assuntos: Alanine Transaminase - blood ; Animals ; Antibodies - therapeutic use ; Aspartate Aminotransferases - blood ; Biological and medical sciences ; Escherichia coli ; Gastroenterology. Liver. Pancreas. Abdomen ; Lipopolysaccharides - toxicity ; Liver - drug effects ; Liver - pathology ; Liver Failure - chemically induced ; Liver Failure - pathology ; Liver Failure - prevention & control ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Macrophage Migration-Inhibitory Factors - antagonists & inhibitors ; Macrophage Migration-Inhibitory Factors - genetics ; Macrophage Migration-Inhibitory Factors - immunology ; Male ; Medical sciences ; Mice ; Mice, Inbred ICR ; Mycobacterium bovis ; Other diseases. Semiology ; Rabbits ; Rats ; Survival Rate ; Transcription, Genetic - drug effects
É parte de: Hepatology (Baltimore, Md.), 1999-06, Vol.29 (6), p.1752-1759
Descrição: During the past few years, the biological functions of macrophage migration inhibitory factor (MIF) have been extensively re‐evaluated. This has been found to be protein involved in broad‐spectrum pathophysiological states as an inflammatory cytokine, pituitary‐derived hormone, and glucocorticoid‐induced immunomodulator. In this study, we investigated the involvement of this cytokine in the pathogenesis of lethal liver injury. Injecting a small dose of lipopolysaccharide (LPS) into bacille Calmette‐Guerin (BCG)‐primed Jcl:ICR mice caused a lethal hepatic injury mimicking fulminant hepatitis, in which 8 of 11 mice died within 48 hours (27% survival rate). Massive necrosis of parenchymal hepatocytes with marked mononuclear cell infiltration was observed by histological examination. Immunohistochemical analysis showed that most of the infiltrating mononuclear cells were Kupffer cells, macrophages, and, to a lesser extent, T cells. In parallel, serum aminotransferase and tumor necrosis factor‐α (TNF‐α) levels were increased. When an anti‐MIF polyclonal antibody (0.3 mg IgG fraction/mouse) was intraperitoneally injected into mice primed with BCG, it protected them from acute hepatic failure (90% survival rate) with concomitant improvement of histological features. Injection of the antibody also suppressed the up‐regulation of TNF‐α and T‐cell infiltration induced by LPS. Taken together, these results suggested that treatment with the anti‐MIF antibody suppresses the endotoxin‐induced fatal hepatic failure by regulating production of inflammatory cytokines and T‐cell infiltration.
Editor: Philadelphia, PA: W.B. Saunders
Idioma: Inglês

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Prevention of lethal acute hepatic failure by antimacrophage migration inhibitory factor antibody in mice treated with bacille calmette‐guerin and lipopolysaccharide

Kobayashi, Seiji ; Nishihira, Jun ; Watanabe, Satoshi ; Todo, Satoru

Philadelphia, PA: W.B. Saunders

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