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Published on: September 9, 2011
Interferon-gamma modifies cytokine release in vitro by monocytes from surgical patients
C Schinkel1, K Licht, S Zedler
1Departments of Surgery, Ludwig-Maximilians University Munich, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany.
Insights
Interferon-gamma (IFN-gamma) modulates monocyte activity, enhancing pro-inflammatory cytokine release post-surgery. While potentially beneficial, its use requires caution in critically ill patients due to its potent inflammatory effects.
Area of Science:
- Immunology
- Critical Care Medicine
- Sepsis Research
Background:
- Interferon-gamma (IFN-gamma) is crucial for monocyte immune function but can worsen sepsis-induced organ failure.
- Its role in modifying monocyte activity before and after injury requires further clarification.
Purpose of the Study:
- To investigate the effects of IFN-gamma on monocyte activation in patients undergoing cardiac surgery.
- To define IFN-gamma's potential as a modifier of monocyte activity in the context of injury and inflammation.
Main Methods:
- Whole blood samples from 19 patients before and after cardiac surgery were incubated with lipopolysaccharide (LPS) and IFN-gamma.
- Plasma levels of pro- and anti-inflammatory cytokines were measured.
Main Results:
- IFN-gamma significantly augmented LPS-induced release of TNF-alpha, IL-6, IL-12, and IL-1Ra, especially postoperatively.
- No significant effect was observed on IL-1beta, neopterin, or soluble TNF-R release.
Conclusions:
- IFN-gamma exhibits a diverse range of effects on monocyte activation, including anti-inflammatory properties.
- Preactivated monocytes show increased reactivity to IFN-gamma, suggesting potential efficacy but necessitating cautious administration in highly inflamed 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.
Conclusion:
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.
