Glutamine decreases inflammation in infant rat endotoxemia.
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.
Garrett-Cox
Robin G
RG
Department of Paediatric Surgery, Institute of Child Health, WC1N 1EH London, United Kingdom.
Stefanutti
Giorgio
G
Booth
Clare
C
Klein
Nigel J
NJ
Pierro
Agostino
A
Eaton
Simon
S
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
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D016753:Interleukin-10; D009569:Nitric Oxide