Arginine-enriched total parenteral nutrition improves survival in peritonitis by normalizing NFkappaB activation in peritoneal resident and exudative leukocytes.
BACKGROUND
Enteral nutrition maintains peritoneal defense more effectively than parenteral nutrition, at least partly by preserving NFkappaB activation in peritoneal cells. We hypothesized that arginine (ARG)-enriched parenteral nutrition would normalize NFkappaB activation in peritoneal leukocytes, thereby improving the survival of peritonitis models.


METHODS
A total of 105 ICR mice were randomized to chow (n=33), IV feeding of a standard (STD) total parenteral nutrition (STD-TPN) solution (ARG 0.3%) (n=35), or 1% ARG-TPN solution (n=37), and fed accordingly for 5 days.Experiment 1: Thirty mice were used for intranuclear NFkappaB measurement in peritoneal resident cells (PRCs). After incubation with lipopolysaccharide (LPS: 0, 1, 10 microg/mL) for 30 minutes, intranuclear NFkappaB activity was examined by laser scanning cytometry.Experiment 2: Fifty-one mice were injected with 2 mL of 1% glycogen intraperitoneally. Peritoneal exudative cells (PECs) were obtained at 2 or 4 hours after glycogen administration for NFkappaB measurement. Cytokine (TNFalpha, IL-10) levels in peritoneal lavage fluid were also determined by ELISA.Experiment 3: After 5 days of feeding, 24 mice underwent cecal ligation and puncture. Survival was observed up to 5 days.


RESULTS
Experiment 1: Intranuclear NFkappaB levels in the ARG-TPN and chow groups increased dose-dependently after LPS stimulation, while the level in the STD-TPN group was unchanged.Experiment 2: Intranuclear NFkappaB level was significantly higher at 2 hours in the chow than in the STD-TPN group, whereas in the ARG-TPN mice the level was midway between those of the chow and STD-TPN groups. TNFalpha and IL-10 levels of the chow group were significantly higher than those of STD-TPN mice at 2 hours. TNFalpha was significantly higher in the ARG-TPN group than in the STD-TPN group, but the IL-10 level showed no recovery.Experiment 3: Survival times were significantly reduced in the STD-TPN as compared with the chow group, though ARG-TPN improved survival.


CONCLUSIONS
ARG-enriched TPN is a surrogate for enteral feeding which maintains peritoneal defense by preserving NFkappaB activation in peritoneal resident and exudative leukocytes.
Ueno
Chikara
C
Department of Surgery, National Defense Medical College, Saitama, Japan.
Fukatsu
Kazuhiko
K
Maeshima
Yoshinori
Y
Moriya
Tomoyuki
T
Omata
Jiro
J
Saitoh
Daizoh
D
Mochizuki
Hidetaka
H
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D016207:Cytokines / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D010289:Parenteral Nutrition, Total; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D010538:Peritonitis / Q000401:mortality*
D016207:Cytokines; D016328:NF-kappa B; D001120:Arginine