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

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.

Figure 1. The ex vivo LPS-stimulated TNF-α production into whole blood was measured 24 hours before surgery, immediately after surgery, and 48 hours after surgery. TNF-α secretion is given as percentage of the changes in comparison to preoperative values. Level of significance P = .02; GLY-GLN vs. control and GLY-GLN vs. ALA-GLN.

Figure 2. The phagocytic capacity of monocytes in whole blood was measured 24 hours before surgery, immediately after surgery, and 48 hours after surgery. Phagocytosis of groups is given as percentage of the changes in comparison to preoperative values.