title: Nutritional route affects ERK phosphorylation and cytokine production in hepatic mononuclear cells.
abstract: OBJECTIVE
  To clarify the influence of nutritional route on hepatic immunity in a murine model.
  
  
  BACKGROUND
  Parenteral nutrition is disadvantageous for preventing infectious complications in critically ill and/or severely injured patients as compared with enteral nutrition. To date, lack of enteral nutrition has been demonstrated to impair mucosal immunity, gut barrier function, and the peritoneal defense system. However, influences of nutritional route on hepatic immunity, another important defense system against infection, have not been well studied.
  
  
  METHODS
  Male ICR mice were randomized to 3 groups: ad libitum chow (chow), intravenous (IV)-TPN and intragastric (IG)-TPN groups. The TPN groups were given isocaloric and isonitrogenous TPN solutions. After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. Hepatic MNC numbers and functions (cytokine production, intracellular signaling, and LPS receptor expression) were determined. Moreover, 1.0 x 10 Pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined.
  
  
  RESULTS
  Hepatic MNC numbers were significantly lower in the IV-TPN group than in the chow and IG-TPN groups, without subpopulation changes. As compared with enterally fed mice, cytokine production (TNF-alpha, IFN-gamma, and IL-10) by hepatic MNCs in response to LPS was impaired in parenterally fed mice in association with blunted phosphorylation of ERK1/2, a MAPK. Hepatic MNCs from IV-TPN mice showed decreased expressions of CD14 and TLR4/MD2, as compared with enterally fed mice. Survival times were reduced in the IV-TPN group as compared with the chow and IG-TPN groups.
  
  
  CONCLUSIONS
  Preservation of hepatic immunity with enteral feeding is important for prevention of infectious complications in severely injured and/or critically ill patients.
authors.affiliation: Department of Surgery I, Chiba University, Chiba, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Moriya
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukatsu
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Fumie
authors.initials: F
authors.lastname: Ikezawa
authors.forename: Chikara
authors.initials: C
authors.lastname: Ueno
authors.forename: Woodae
authors.initials: W
authors.lastname: Kang
authors.forename: Eiji
authors.initials: E
authors.lastname: Takakayama
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D016638:Critical Illness; D016207:Cytokines / Q000378:metabolism*; D004750:Enteral Nutrition; D007728:Kupffer Cells / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018529:Nutritional Support; D010289:Parenteral Nutrition, Total; D010766:Phosphorylation; D018805:Sepsis / Q000276:immunology*
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3