title: Anti-tumor necrosis factor-α monoclonal antibody alleviates parenteral nutrition-associated liver disease in mice.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Nutrition Center, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Gong
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069285:Infliximab; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010288:Parenteral Nutrition / Q000009:adverse effects*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490549:Abcb11 protein, mouse; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D001647:Bile Acids and Salts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000410:Alanine Transaminase; D001663:Bilirubin