Interferon-gamma modifies cytokine release in vitro by monocytes from surgical patients.
BACKGROUND
Treatment with interferon-gamma (IFN-gamma), a key mediator for adequate forward-regulatory monocyte immune capability, has been advocated to overcome posttraumatic mononuclear leukocyte paralysis. Conversely, IFN-gamma also is a potent proinflammatory mediator contributing to capillary leakage in sepsis-driven organ failure. The objective of this investigation was to further define the potential of IFN-gamma as a modifier of monocyte activity before and after injury.


METHODS
Whole blood samples from 19 patients (7 female and 12 male patients; age, 68 +/- 5 years) before and after cardiac surgery with extracorporeal circulation were incubated under continuous rotation with lipopolysaccharide for 12 hours in the presence or absence of human recombinant IFN-gamma. Pro- and anti-inflammatory cytokines were determined in the plasma.


RESULTS
Lipopolysaccharide-induced release of tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-1Ra, and prostaglandin E2 was clearly augmented with IFN-gamma most strikingly postoperatively (p < 0.05). There was no effect on IL-1beta, neopterin, and soluble tumor necrosis factor-R release.


CONCLUSIONS
Thus there is a wide spectrum of IFN-gamma activity on monocyte activation including anti-inflammatory properties. Since cellular preactivation facilitates monocyte reactivity toward IFN-gamma, we conclude that exogenous administration should be effective but must be carried out with great caution in patients with profound inflammation.
Departments of Surgery, Ludwig-Maximilians University Munich, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany.
C
C
Schinkel
K
K
Licht
S
S
Zedler
S
S
Schinkel
P
P
Fraunberger
D
D
Fuchs
E
E
Neugebauer
E
E
Kreuzer
E
E
Faist
D000368:Aged; D006348:Cardiac Surgical Procedures; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000503:physiopathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone