In vitro restoration of post-operatively decreased IFN-gamma levels after cardiac surgery and its effect on pro- and anti-inflammatory mediators.
BACKGROUND
A decreased synthesis of interferon gamma (IFN-gamma) by TH 1 lymphocytes after cardiac operations with cardiopulmonary bypass (CPB) is part of the inflammatory response to local operative and systemic traumas. The consequences of this mechanism on the release of pro- and anti-inflammatory cytokines remain unclear. To evaluate the role of IFN-gamma, we added recombinant IFN-gamma to peripheral blood mononuclear cells (PBMCs) on the first post-operative day in an attempt to restore pre-operative values and then measured the release of pro- and anti-inflammatory cytokines in vitro.


METHODS
PBMCs of 10 patients scheduled for elective coronary artery bypass grafting (CABG) were obtained pre-operatively (d0) and on the first (d1) and third (d3) post-operative days. The release of IL-6, IL-8, TNF-alpha, IFN-gamma, IL-10, IL-2, and IL-4 was studied after stimulation (48 h) with PHA (phytohemagglutinin) and LPS (lipopolysaccharide) in the absence or presence of recombinant human IFN-gamma.


RESULTS
Endogenous IFN-gamma synthesis was suppressed on d1. Adding exogenous IFN-gamma restored IFN-gamma levels to normal on d1 and doubled IFN-gamma levels on d0 and d3. The addition of IFN-gamma increased TNF-alpha levels up to 250% on d1 and IL-2 synthesis by 75% on d1 and d3; the IL-2 levels, however, were still significantly depressed. The addition of recombinant IFN-gamma did not affect the synthesis of IL-6, IL-8, IL-10, and IL-4.


CONCLUSIONS
Contrary to our expectations, the in vitro release of IL-6 and IL-8 as well as IL-10 and IL-4 was not influenced by the addition of IFN-gamma. However, TNF-alpha production in isolated PBMC cultures increased significantly on the first post-operative day. This may indicate a hyper-reactivity of PBMCs to IFN-gamma and suggests that the decrease in IFN-gamma synthesis might prevent an excessive stimulation of the non-specific immune system by high TNF-alpha levels after cardiac surgery.
Franke
Axel
A
Department of Cardiovascular Surgery, Bundeswehr Central Hospital, Koblenz, Germany. dr.axel.franke@t-online.de
Lante
Wolfgang
W
Markewitz
Andreas
A
Weinhold
Christian
C
D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma