title: The influence of dietary restriction on hepatic mononuclear cell numbers and functions in mice.
abstract: BACKGROUND
  Surgical patients with gastrointestinal malignancies are at increased risk for malnutrition. However, the mechanism by which dietary restriction (DR), one form of malnutrition, impairs hepatic immunity remains to be clarified. The present study was designed to examine the influence of DR on hepatic mononuclear cell (MNC) numbers, subpopulations, and cytokine productions (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ], and interleukin 10 [IL-10]) in response to lipopolysaccharide (LPS) in mice. Immunoglobulin (Ig) A levels in the gallbladder and histopathologic changes in the liver were also assessed.
  
  
  METHODS
  Male Institute of Cancer Research mice were randomly assigned to three dietary groups: ad libitum (AD), mild restriction (MR), and severe restriction (SR). The AD, MR, and SR groups received daily mouse chow in amounts of 190, 133, and 76 g/kg, respectively, for 7 d. After the mice had been fed for 7 d, hepatic MNCs were isolated. Total hepatic MNCs were counted and subpopulations were determined by flow cytometry. Cytokine productions (TNF-α, IFN-γ, and IL-10) by hepatic MNCs in response to LPS were measured. Blood samples were analyzed for hepatobiliary biochemical parameters. IgA levels in gallbladder bile were measured with enzyme-linked immunosorbent assay. In addition, liver histologies were examined.
  
  
  RESULTS
  Hepatic MNC numbers were significantly lower in the MR and SR groups than in the AD group, with no significant difference between the MR and SR groups. The percentage of B cells was significantly lower in the SR group than in the MR and AD groups, whereas the T-cell percentage was higher in the SR group than in the MR and AD groups. The percentage of Kupffer cells was significantly lower in the SR group than in the AD group, whereas that in the MR group was midway between those in the SR and AD groups. TNF-α and IL-10 levels in hepatic MNC culture supernatants were increased LPS-dose dependently in the AD group. However, the increase was slight in the MR group and absent in the SR group. The IgA levels in gallbladder bile were significantly lower in the SR and MR groups than in the AD group. On the basis of hematoxylin and eosin staining of hepatic sections, livers from the SR group showed atrophic hepatocytes and sinusoidal dilatation, whereas these changes were absent in the AD group.
  
  
  CONCLUSIONS
  DR decreases hepatic MNC number with subpopulation changes, reduces IgA levels in gallbladder bile, blunts cytokine production by hepatic MNCs, and induces pathologic damage in the liver, which may be an important mechanism underlying the impaired host defense associated with malnutrition.
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan. Electronic address: tmoriya@ndmc.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Moriya
authors.affiliation: Surgical Center, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukatsu
authors.affiliation: Department of Pathology, National Defense Medical College, Saitama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.affiliation: Division of Traumatology, National Defense Medical College Research Institute, Saitama, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Division of Traumatology, National Defense Medical College Research Institute, Saitama, Japan.
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.affiliation: Department of Surgery, Chiba University, Chiba, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000096:biosynthesis; D004038:Diet, Reducing; D007070:Immunoglobulin A / Q000032:analysis; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008099:Liver / Q000276:immunology*; D008297:Male; D044342:Malnutrition / Q000276:immunology*; D051379:Mice; D009929:Organ Size
chemical_list: D016207:Cytokines; D007070:Immunoglobulin A; D000410:Alanine Transaminase
keywords: Cytokine response; Immunity; Immunoglobulin; Liver; Nutrition