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.

Conclusion: ARG-enriched TPN is a surrogate for enteral feeding which maintains peritoneal defense by preserving NFkappaB activation in peritoneal resident and exudative leukocytes.