Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression: accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response

Ann Surg. 2003 Jan;237(1):110-5. doi: 10.1097/00000658-200301000-00015.

Abstract

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.

Summary background data: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / surgery*
  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers / analysis
  • Dipeptides / therapeutic use*
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immune Tolerance / drug effects*
  • Immunosuppression Therapy
  • Infusions, Intravenous
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Perioperative Care
  • Postoperative Complications / immunology*
  • Postoperative Complications / prevention & control
  • Probability
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / drug effects

Substances

  • Biomarkers
  • Dipeptides
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • glycylglutamine
  • alanylglutamine