Anti-tumor necrosis factor-α monoclonal antibody alleviates parenteral nutrition-associated liver disease in mice.

The authors aimed to investigate the role of anti-tumor necrosis factor (TNF)-α monoclonal antibody treatment in a mouse model of parenteral nutrition-associated liver disease (PNALD). C57BL/6J male mice (aged 6-8 weeks) were randomly assigned to 3 groups: parenteral nutrition (PN), PN with anti-TNF-α monoclonal antibody treatment (PN + mAb), and controls. A central venous catheter was inserted for intravenous infusion of a PN solution (PN and PN + mAb groups) or saline (controls) for 7 days. Liver pathology, hepatic biochemical indicators, and serum TNF-α concentrations were analyzed. Levels of hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA were also evaluated in each group. The PN group showed significant increases in serum transaminase, direct bilirubin, and bile acids relative to the control group (P < .05). Histopathological changes in this group were consistent with early stage cholestasis. The pathological score and serum alanine aminotransferase, total bilirubin, and direct bilirubin levels were improved in the PN + mAb group relative to the PN group (P < .05). The PN group showed significantly lower hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA expression than the controls (P < .05), but these were significantly increased compared to the PN group (P < .05). Infliximab administered at a single dose of 5 mg/kg body weight ameliorated the progression of PNALD and improved the expression of hepatic ABC transporter genes. Therefore, anti-TNF-α monoclonal antibody may be a beneficial therapy for patients with PNALD.

Citation

Jing Li, Yi-Ming Gong, Jiang Wu, Wen-jie Wu, Wei Cai. Anti-tumor necrosis factor-α monoclonal antibody alleviates parenteral nutrition-associated liver disease in mice. JPEN. Journal of parenteral and enteral nutrition. 2012 Mar;36(2):219-25

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PMID: 22275328

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