Postoperative PMBC-derived IL-6 and TNF-alpha-release is uninfluenced by IL-12-mediated restoration of IFN-gamma synthesis.
OBJECTIVE
Interferon gamma (IFN-gamma) synthesis in peripheral blood mononuclear cells (PBMCs) is suppressed after major surgical trauma. Interleukin-12 (IL-12) has been shown to stimulate IFN-gamma-synthesis. We hypothesised that exogenous IL-12 can increase perioperative pro-inflammatory cytokine release. We therefore assessed the effect of IL-12 on IFN-gamma-synthesis and pro-inflammatory cytokine release in vitro before and after cardiac surgery.


METHODS
In this prospective study, PBMCs from 20 elective cardiac surgery patients were stimulated for 24 hours with staphylococcal enterotoxin B and lipopolysaccharide before surgery (d0) and on the 1st (d1), 3rd (d3) and 5th (d5) postoperative days. IL-12 was added at each time point investigated. IFN-gamma, IL-6, tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4, IL-5, and IL-10 concentrations were assayed.


RESULTS
IFN-gamma-synthesis was significantly reduced at d1, d3 and d5. When IL-12 was added, IFN-gamma-synthesis returned to preoperative levels at d1, d3 and d5. Neither IL-6 nor TNF-alpha-synthesis was influenced by IL-12.


CONCLUSIONS
IFN-gamma synthesis is significantly reduced after major surgical trauma. IL-12 increases IFN-gamma-synthesis before and after surgery without influencing pro-inflammatory cytokine synthesis.
Franke
Axel
A
Department of Cardiovascular Surgery, German Armed Forces Central Hospital, Koblenz, Germany. dr.axel.franke@t-online.de
Lante
Wolfgang
W
Kurig
Edmond
E
Zoeller
Lothar G
LG
Kollig
Erwin
E
Markewitz
Andreas
A
D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004768:Enterotoxins; C508609:IL10 protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; C508599:IL5 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma