Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression: accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response.
OBJECTIVE
To investigate whether the administration of different glutamine-containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has a differing impact on perioperative immunomodulation.


BACKGROUND
Surgery leads to transitory immunosuppression, which is associated with decreased plasma glutamine (GLN) levels and increased susceptibility to infection and sepsis. A useful tool to detect immunocompetence is the ex vivo lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) secretion in whole blood.


METHODS
Forty-five patients undergoing major abdominal surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino acid solution; control group) as a continuous infusion over 72 hours, starting 24 hours before surgery. Blood samples were collected before infusion, at the end of surgery, and 48 hours postoperatively to determine the TNF-alpha release into whole blood stimulated with LPS. Groups were compared by analysis of variance.


RESULTS
The groups were comparable in age, gender distribution, and length of operative time. At the end of surgery a significant reduction in ex vivo LPS-stimulated TNF-alpha production was observed in all groups. In patients who received GLY-GLN, the induced TNF-alpha production was restored after 48 hours.


CONCLUSIONS
In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.
Exner
Ruth
R
Surgical Research Laboratories, University of Vienna, Austria.
Tamandl
Dietmar
D
Goetzinger
Peter
P
Mittlboeck
Martina
M
Fuegger
Reinhold
R
Sautner
Thomas
T
Spittler
Andreas
A
Roth
Erich
E
D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D004151:Dipeptides / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007165:Immunosuppression Therapy; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D011336:Probability; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000187:drug effects
D015415:Biomarkers; D004151:Dipeptides; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C039788:glycylglutamine; C054122:alanylglutamine