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-gamma (IFN-gamma)? METHODS: The study included 35 patients with sepsis after major visceral surgery and 85 control patients. Monocyte secretion of interleukin (IL)-1 beta, IL-12 p40 and p70, IL-18, tumor necrosing factor, and IL-10 with or without IFN-gamma 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-1 beta, 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-1 beta secretion, but not of IL-10 production, correlated with survival. Despite the exposure of monocytes in vitro to IFN-gamma for 16 hours, the production of the biologically active IL-12 p70 heterodimer was severely suppressed both in survivors and nonsurvivors, although the secretion of the p40 subunit was restored. In contrast, IFN-gamma treatment resulted in a significant suppression of monocyte IL-1 beta 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 pro- and 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-gamma did not reconstitute defective proinflammatory cytokine production.
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-gamma (IFN-gamma)? METHODS: The study included 35 patients with sepsis after major visceral surgery and 85 control patients. Monocyte secretion of interleukin (IL)-1 beta, IL-12 p40 and p70, IL-18, tumor necrosing factor, and IL-10 with or without IFN-gamma 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-1 beta, 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-1 beta secretion, but not of IL-10 production, correlated with survival. Despite the exposure of monocytes in vitro to IFN-gamma for 16 hours, the production of the biologically active IL-12 p70 heterodimer was severely suppressed both in survivors and nonsurvivors, although the secretion of the p40 subunit was restored. In contrast, IFN-gamma treatment resulted in a significant suppression of monocyte IL-1 beta 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 pro- and 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-gamma did not reconstitute defective proinflammatory cytokine production.
Authors: Karel G M Beenakker; Rudi G J Westendorp; Anton J M de Craen; Sijia Chen; Yotam Raz; Bart E P B Ballieux; Rob G H H Nelissen; Alexander F L Later; Tom W Huizinga; Pieternella E Slagboom; Dorret I Boomsma; Andrea B Maier Journal: J Innate Immun Date: 2019-06-21 Impact factor: 7.349
Authors: Spaska A Stanilova; Zhivko T Karakolev; Gospodin S Dimov; Zlatka G Dobreva; Lyuba D Miteva; Emil S Slavov; Chavdar S Stefanov; Noyko S Stanilov Journal: Intensive Care Med Date: 2005-02-18 Impact factor: 17.440
Authors: Hina Chaudhry; Juhua Zhou; Yin Zhong; Mir Mustafa Ali; Franklin McGuire; Prakash S Nagarkatti; Mitzi Nagarkatti Journal: In Vivo Date: 2013 Nov-Dec Impact factor: 2.155
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