Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression on monocytes.
OBJECTIVE
Surgery, trauma and inflammation reduce HLA-DR expression on monocytes, which is associated with an increased susceptibility to infection and sepsis. Furthermore, surgery decreases plasma glutamine (GLN) levels. The expression of HLA-DR on human monocytes in vitro is dependent on the concentration of GLN in the culture medium. We therefore hypothesized that postoperative infusions of glutamine-dipeptides would prevent the decreased HLA-DR expression on monocytes.


METHODS
Thirty patients undergoing major abdominal surgery were randomly allocated to receive either 1500 ml Vamin (control) or an isonitrogenic formulation containing Vamin and 500 ml glycyl-glutamine (35 g GLN; 0.5g/kg BW) (GLY-GLN), or Vamin and 500 ml alanyl-glutamine (35 g GLN; 0.5 g/kg BW) (ALA-GLN) as a continuous infusion over 48 h post-operatively. Immediately and 48 h after surgery blood samples were collected to determine HLA-DR expression on monocytes by flow cytometry.


RESULTS
The groups were comparable with respect to age, gender distribution and operation time. In patients receiving GLY-GLN mean HLA-DR expression on monocytes at 48 h was significantly better preserved than in controls (65.0 %+/-7 % vs 42.5 %+/-4 %;P<0.05), whereas HLA-DR expression on monocytes in patients receiving ALA-GLN was not significantly different.


CONCLUSIONS
This is the first study comparing the dipeptides GLY-GLN and ALA-GLN in the postoperative setting. The GLY-GLN induced preservation of HLA-DR on monocytes following surgery may prevent infectious complications in these patients.
Spittler
A
A
Surgical Research Laboratories, AKH, University of Vienna, Wachringer Guertel 19-20, 1090 Vienna, Austria.
Sautner
T
T
Gornikiewicz
A
A
Manhart
N
N
Oehler
R
R
Bergmann
M
M
Függer
R
R
Roth
E
E
D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage / Q000097:blood; D004151:Dipeptides / Q000008:administration & dosage*; D004573:Electrolytes; D005260:Female; D005434:Flow Cytometry; D005947:Glucose; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007165:Immunosuppression Therapy; D007263:Infusions, Parenteral; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D057947:Parenteral Nutrition Solutions; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D018805:Sepsis / Q000276:immunology* / Q000517:prevention & control; D012996:Solutions; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000596:Amino Acids; D004151:Dipeptides; D004573:Electrolytes; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D057947:Parenteral Nutrition Solutions; D012996:Solutions; D014409:Tumor Necrosis Factor-alpha; C545824:amino-acid, glucose, and electrolyte solution; C039788:glycylglutamine; D005947:Glucose; C054122:alanylglutamine