Sepsis after major visceral surgery is associated with sustained and interferon-γ-resistant defects of monocyte cytokine production

Heike Weighardt, Claus Dieter Heidecke, Klaus Emmanuilidis, Stefan Maier, Holger Bartels, Jörg Rüdiger Siewert, Bernhard Holzmann

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95 Scopus citations

Abstract

Background. Recent clinical trials failed to demonstrate beneficial effects of anti-inflammatory sepsis therapy. The present study therefore asked the following questions: Is there evidence for immunosuppression during postoperative sepsis? When, during the septic course, may immunosuppression develop? Can defective cellular functions be restored by in vitro treatment with interferon-γ (IFN-γ)? Methods. The study included 35 patients with sepsis after major visceral surgery and 85 control patients. Monocyte secretion of interleukin (IL)-Iβ, IL-12 p40 and p 70, IL-18, tumor necrosing factor, and IL-10 with or without IFN-γ treatment and its correlation with the course and outcome of postoperative sepsis were determined. Results. Postoperative sepsis was associated with an immediate defect of endotoxin- stimulated monocyte production of IL-12 p40, IL-1β, and IL-10 in both surviving and nonsurviving patients. During the final phase of postoperative sepsis, a significant recovery of IL-12 p40 and IL-1β secretion, but not of IL-10 production, correlated with survival. Despite the exposure of monocytes in vitro to IFN-γ for 16 hours, the production of the biologically active IL-12 p 70 heterodimer was severely suppressed both in survivors and nonsurvivors, although the secretion of the p40 subunit was restored. In contrast, IFN-γ treatment resulted in a significant suppression of monocyte IL-1β production in all patient subgroups. Alterations of monocyte tumor necrosing factor secretion were not observed. The production of IL-18 was below the limits of detection in all samples. Conclusions. Postoperative sepsis was associated with immediate monocyte defects that affected both proand anti-inflammatory cytokine secretion, which suggests that immunosuppression is a primary rather than a compensatory response to a septic challenge. Sepsis survival correlated with the recovery of the proinflammatory, but not the anti-inflammatory, response. The treatment of monocytes with IFN-γ did not reconstitute defective proinflammatory cytokine production.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalSurgery
Volume127
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

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