Is interferon gamma suppression after cardiac surgery caused by a decreased interleukin-12 synthesis?
BACKGROUND
The suppression of interferon gamma (IFN-gamma) synthesis after cardiac surgery is discussed as a cause of postoperative immunosuppression that predisposes to postoperative infectious complications. Because several studies have suggested that interleukin-12 (IL-12) production by monocytes and macrophages is reduced after cardiac surgery, this might cause a decrease in IFN-gamma release. To better understand these processes, we assessed the role of IL-12 in IFN-gamma synthesis in vitro before and after cardiac surgery.


METHODS
Heparinized whole blood samples were obtained from 20 patients undergoing elective cardiac surgery preoperatively (day 0) and on the first (day 1), third (day 3), and fifth (day 5) postoperative days, and stimulated (24 hours) with staphylococcal enterotoxin B and lipopolysaccharide. Recombinant IL-12 was added at each time point investigated. Interferon-gamma, IL-12, IL-2, IL-4, and IL-5 concentrations and histocompatibility leukocyte antigen-DR (HLA-DR) expression on monocytes and macrophages were assayed by flow cytometry.


RESULTS
The HLA-DR expression, IL-12 release, and IFN-gamma synthesis were significantly reduced on day 1, day 3, and day 5. Recovery began on day 3. Interleukin-12 caused a significant increase in IFN-gamma synthesis at each time point. When IL-12 was added, IFN-gamma synthesis returned to preoperative levels on days 3 and 5.


CONCLUSIONS
The synthesis of IFN-gamma is significantly reduced after cardiac surgery. The application of IL-12 causes an increase in IFN-gamma synthesis before surgery and a return of IFN-gamma to preoperative levels within a few days after surgery. These findings suggest that postoperative suppression of IFN-gamma release is caused by a decrease in IL-12 synthesis. In addition, IL-12 has a mainly proinflammatory effect both before and after surgery.
Franke
Axel
A
Department of Cardiovascular Surgery, Bundeswehr Central Hospital, Koblenz, Germany. dr.axel.franke@t-online.de
Lante
Wolfgang
W
Kurig
Edmond
E
Zöller
Lothar G
LG
Weinhold
Christian
C
Markewitz
Andreas
A
D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004198:Disease Susceptibility; D015536:Down-Regulation / Q000502:physiology*; D017558:Elective Surgical Procedures; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007239:Infections / Q000453:epidemiology / Q000209:etiology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology; D011184:Postoperative Period; D011994:Recombinant Proteins / Q000494:pharmacology
D004768:Enterotoxins; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015848:Interleukin-5; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma