The effect of glutamine infusion on the inflammatory response and HSP70 during human experimental endotoxaemia.
BACKGROUND
Glutamine supplementation has beneficial effects on morbidity and mortality in critically ill patients, possibly in part through an attenuation of the proinflammatory cytokine response and a stimulation of heat shock protein (HSP)70. We infused either alanine-glutamine or saline during endotoxin challenge and measured plasma cytokines and HSP70 protein expression.


METHODS
This crossover study, conducted in eight healthy young men, was double-blind, randomized and placebo-controlled. It was performed on 2 trial days, separated by a 4-week washout period. The volunteers received an infusion of alanine-glutamine at a rate of 0.025 g/(kg body weight x hour) or saline for 10 hours. After 2 hours, an intravenous bolus of Escherichia coli endotoxin (0.3 ng/kg) was administered. Blood samples were collected hourly for the following 8 hours. HSP70 protein content in isolated blood mononuclear cells (BMNCs) was measured by Western blotting.


RESULTS
Plasma glutamine increased during alanine-glutamine infusion. Endotoxin reduced plasma glutamine during both trials, but plasma glutamine levels remained above baseline with alanine-glutamine supplementation. Endotoxin injection was associated with alterations in white blood cell and differential counts, tumour necrosis factor-alpha, IL-6, temperature and heart rate, but glutamine affected neither the endotoxin-induced change in these variables nor the expression of HSP70 in BMNCs.


CONCLUSIONS
Endotoxin reduced plasma glutamine independently of alanine-glutamine infusion, but supplementation allows plasma levels to be maintained above baseline. Glutamine alters neither endotoxin-induced systemic inflammation nor early expression of HSP70 in BMNCs.


BACKGROUND
ClinicalTrials.gov ID: NCT 00780520.
Andreasen
Anne Sofie
AS
Department of Infectious Diseases, Faculty of Health Sciences, University of Copenhagen, The Centre of Inflammation and Metabolism, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark. sofie_andreasen@msn.com
Pedersen-Skovsgaard
Theis
T
Mortensen
Ole Hartvig
OH
van Hall
Gerrit
G
Moseley
Pope Lloyd
PL
Pedersen
Bente Klarlund
BK
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced; D004731:Endotoxins / Q000633:toxicity; D005973:Glutamine / Q000008:administration & dosage* / Q000097:blood*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced; D018836:Inflammation Mediators / Q000097:blood*; D007262:Infusions, Intravenous; D008297:Male; D055815:Young Adult
D004731:Endotoxins; D018840:HSP70 Heat-Shock Proteins; D018836:Inflammation Mediators; D005973:Glutamine