Nutritional route affects ERK phosphorylation and cytokine production in hepatic mononuclear cells.
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.
Moriya
Tomoyuki
T
Department of Surgery I, Chiba University, Chiba, Japan.
Fukatsu
Kazuhiko
K
Maeshima
Yoshinori
Y
Ikezawa
Fumie
F
Ueno
Chikara
C
Kang
Woodae
W
Takakayama
Eiji
E
Saitoh
Daizoh
D
Mochizuki
Hidetaka
H
Miyazaki
Masaru
M
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*
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3