title: The effect of adding fish oil to parenteral nutrition on hepatic mononuclear cell function and survival after intraportal bacterial challenge in mice.
abstract: BACKGROUND
  Parenteral nutrition (PN) is indispensable for meeting caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition; however, PN impairs hepatic immunity. We examined the effects of ω-3 and -6 polyunsaturated fatty acids, added individually to fat-free PN, on hepatic immunity in a murine model. We focused on serum liver enzymes, cytokine production, histopathology, and the outcomes after intraportal bacterial challenge.
  
  
  METHODS
  Male Institute of Cancer Research mice were randomized into 4 groups; ad libitum chow (CHOW), fat-free PN (FF-PN), PN + fish oil (FO-PN), or PN + safflower oil (SO-PN). After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. The number of MNCs was counted and cytokine production (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by hepatic MNCs in response to lipopolysaccharide (LPS) was measured. Blood samples were analyzed for hepatobiliary biochemical parameters. Moreover, 1.0 × 10(7) pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined.
  
  
  RESULTS
  Hepatic MNC numbers were significantly less in the FO-PN and FF-PN than in the CHOW group, whereas the SO-PN group showed moderate recovery of hepatic MNC numbers. The CHOW, FO-PN, and SO-PN groups showed LPS dose-dependent increases in TNF-α levels. These increases were blunted in the FF-PN group. IL-10 levels were increased LPS dose-dependently in the CHOW and FO-PN groups, but no marked changes were observed with LPS stimulation in the SO-PN and FF-PN groups. Plasma levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly greater in the FF-PN than in the FO- and SO-PN and CHOW groups. The FO-PN group showed significantly improved survival compared with the SO-PN and FF-PN groups, showing essentially no morphologic hepatic abnormalities.
  
  
  CONCLUSIONS
  Addition of fish oil to PN was advantageous in terms of reversing PN-induced deterioration of hepatic immunity, as reflected by altered cytokine production. Fish oil administration was also useful for preventing PN-induced hepatobiliary dysfunction. These changes seem to result in better survival and to protect against severe tissue damage after intraportal bacterial challenge. This therapy may have the potential to ameliorate PN-induced impairment of host immunity and thereby decrease morbidity and mortality.
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan. tmoriya@ndmc.ac.jp
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: Yojiro
authors.initials: Y
authors.lastname: Hashiguchi
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
authors.forename: Junji
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000276:immunology*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000276:immunology*; D005395:Fish Oils / Q000008:administration & dosage / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010288:Parenteral Nutrition / Q000009:adverse effects / Q000379:methods*; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011897:Random Allocation; D012450:Safflower Oil / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D008070:Lipopolysaccharides; D012450:Safflower Oil