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Am J Physiol Gastrointest Liver Physiol (January 15, 2004). doi:10.1152/ajpgi.00493.2003
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Submitted on November 21, 2003
Accepted on January 8, 2004

Glutamine Decreases Lipopolysaccharide-Induced Intestinal Inflammation in Infant Rats

Nan Li1, Kellym Liboni1, Mao Zhong Fang1, Don Samuelson2, Patricia Lewis2, Roshan Patel1, and Josef Neu1*

1 Department of Pediatrics, University of Florida, College of Medicine, Gainesville, FL, USA
2 Division of Neonatology, University of Florida, College of Medicine, Gainesville, FL, USA

* To whom correspondence should be addressed. E-mail: neuj{at}peds.ufl.edu.

Using a gastrostomy-fed (GF) rat infant "pup-in-a-cup" model, the effects of protein deprivation and supplemental glutamine (Gln) and glutamate (Glu) were examined in order to test the hypothesis that Gln decreases the pro-inflammatory response induced by LPS in the developing infant rat small intestine. Four groups of 6-7d old pups were fed a rat milk substitute (RMS), one providing 100% and 3 providing 25% of normal protein intake for another 6d. Two of the 25% protein fed groups received supplemental Gln or Glu. GF and LPS treatment blunted body growth and intestinal villus height and increased intestinal cytokine-induced neutrophil chemoattractant (CINC) mRNA in the protein deprivated , non-Gln treated group compared to mother-fed pups (p<0.05). Gln blunted intestinal CINC mRNA (p<0.05) but Glu did not. Intestinal CINC peptide in the LPS treated pups provided 100% and 25% protein was elevated about 13 fold compared to the mother reared pups (p< 0.001). Gln and Glu decreased intestinal CINC peptide by 73 and 80%, respectively. GF, LPS treated pups also had a higher level of plasma CINC peptide (p<0.05). Gln, but not Glu decreased plasma CINC peptide (p<0.05). An approximate 6-fold elevation of intestinal myeloperoxidase (MPO) activity in the GF, LPS treated rats was decreased by Gln and Glu by 92% (p<0.001) and 54% (p<0.05), respectively. Intestinal and plasma TNF{alpha} were increased in GF, LPS treated pups (p<0.01), and Gln and Glu both blunted this increase (p<0.05) in the intestine, but not in the plasma. The results indicate that Gln decreases the LPS-induced inflammatory response in infant rat intestine under different conditions of protein intake.




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