title: Glutamine decreases inflammation in infant rat endotoxemia.
abstract: Glutamine may have benefits during neonatal sepsis, but its effects on systemic inflammation are unknown. Our aim was to determine whether glutamine affects inflammation in neonatal endotoxemia. Eleven-day rat pups were given intraperitoneal injections of saline (control; C), endotoxin (300 microg/g Escherichia coli lipopolysaccharide) (E), saline with glutamine (2 mmol/g; G), or endotoxin with glutamine (EG). Animals were killed after 2 or 6 hours. Plasma glutamine (mmol/L) was measured enzymatically, and both tumor necrosis factor alpha (pg/mL) and interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay. Results, expressed as mean +/- SEM, were analyzed by analysis of variance. Endotoxemia caused a rapid significant decrease in plasma glutamine at 2 hours (C, 0.73 +/- 0.06; E, 0.32 +/- 0.07; mean difference, 0.41 [95% confidence interval {CI, 0.17-0.64}]; P < .001), which was prevented by intraperitoneal glutamine (EG, 0.59 +/- 0.04; mean difference vs E, 0.27 mmol/L [95% CI, 0.03-0.50]; P < .05), indicating glutamine absorption, whereas CG animals had a plasma glutamine of 0.82 +/- 0.07. Tumor necrosis factor alpha was greatly increased by 2-hour endotoxemia (C, 27 +/- 7; E, 2247 +/- 43; mean difference, 2220 pg/mL [95% CI, 2012-2429]; P < .001), and this increase was partly prevented by glutamine (EG, 1991 +/- 91; P < .05 vs E; mean difference, 256; 95% CI, 47-465; P < .05). The effect of glutamine was more pronounced at 6 hours (C, 32 +/- 27; E, 799 +/- 193; EG, 219 +/- 75, C vs E mean difference, 767; 95% CI, 346-1188; P < .001; E vs EG mean difference, 580; 95% CI, 159-1001; P < .01). The IL-10 levels were also greatly increased by 2-hour endotoxemia (C = 55 +/- 21, E = 2429 +/- 58, EG = 1989 +/- 177; C vs E mean difference, 2374; 95% CI, 2740-2008; P < .001; E vs EG mean difference, 440; 95% CI, 74-807; P < .05). Glutamine administration partially prevents the sepsis-induced fall in plasma glutamine levels and reduces the concentration of both proinflammatory and antiinflammatory cytokines.
authors.affiliation: Department of Paediatric Surgery, Institute of Child Health, WC1N 1EH London, United Kingdom.
authors.forename: Robin G
authors.initials: RG
authors.lastname: Garrett-Cox
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stefanutti
authors.forename: Clare
authors.initials: C
authors.lastname: Booth
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Klein
authors.forename: Agostino
authors.initials: A
authors.lastname: Pierro
authors.forename: Simon
authors.initials: S
authors.lastname: Eaton
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood* / Q000276:immunology; D004926:Escherichia coli; D004927:Escherichia coli Infections; D005973:Glutamine / Q000097:blood / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000097:blood; D015227:Lipid Peroxidation; D008930:Mitochondria, Liver / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D016753:Interleukin-10; D009569:Nitric Oxide