Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock

Sfeir, T; Saha, Dhanonjoy C.; Astiz, Mark E.; Rackow, Eric C.

doi:10.1097/00003246-200101000-00026

Cited by 93 publications

(66 citation statements)

References 26 publications

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“…The association of an anti-inflammatory profile with an unfavourable outcome has previously been described in febrile adults with community acquired infections [5]. An anti-inflammatory phenotype is recognised as a hallmark of the "immune paralysis" described in patients with severe sepsis and septic shock [14,15] and more recently a lower basal TNF-α/IL-10 ratio has been demonstrated in patients with septic shock [16]. Our results are consistent with this.…”

Section: Discussionsupporting

confidence: 91%

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

et al. 2005

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Objective-This study aimed to determine whether an anti-inflammatory profile in meningococcal disease is associated with an increased risk of severe disease or septic shock.Design and setting-Prospective observational study in a tertiary care children's hospital. Patients and participants-63 children with confirmed meningococcal disease.Interventions-Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF) were assayed on admission. Receiver operator characteristic curve analysis was used to determine optimum thresholds for IL-1Ra:TNF, IL-1Ra:IL-6 and IL-1Ra:IL-8 ratios.Measurements and results-Median IL-1Ra:TNF and IL-1Ra:IL-6 ratios were significantly higher in severe disease with septic shock than in severe disease without septic shock and in non severe disease (IL-1Ra:TNF 263 vs. 185 vs. 108; IL-1Ra:IL-6 139 vs. 23 vs. 17). Median IL-1Ra:IL-8 ratios were not significantly different in the three groups. A significantly larger proportion of children with high IL-1Ra:TNF-α and IL-1Ra:IL-6 ratios developed severe disease with septic shock than those with a low ratios (95.2% vs. 4.8%; 76.2% vs. 23 .8%).Conclusions-An anti-inflammatory profile appears to be associated with the development of severe disease and septic shock in meningococcal sepsis. This may imply that experimental new therapies of pro-inflammatory cytokine inhibition and anti-inflammatory cytokines in meningococcal disease could be detrimental.

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Section: Discussionsupporting

confidence: 91%

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

et al. 2005

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“…These results suggest that IL-10 might be more important than TGF-β in the pathophysiology of sepsis-induced immunoparalysis. This is in accordance with experimental data showing that blocking IL-10 is more efficient than blocking TGF-β in reversing endotoxin tolerance (59,61,62).…”

Section: Measurement Of Circulating Mediatorssupporting

confidence: 92%

“…They observed that high IL-10 levels were associated with mortality after severe sepsis and, importantly, with stress-induced hyperglycemia, whereas TNF-α, IL-6, and TGF-β concentrations did not have any predictive value. Given the properties of IL-10 in suppressing the synthesis of numerous proinflammatory cytokines (59), its continued release may contribute to the immune dysfunctions observed after septic shock and thus may augment susceptibility to secondary microbial invasion (58)(59)(60).…”

Section: Measurement Of Circulating Mediatorsmentioning

confidence: 99%

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Monneret

Venet

Pachot

et al. 2008

Mol Med

306

323

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“…1, C and D). Although the down-regulation of proinflammatory cytokines like TNF-␣, IL-1, and IL-6 and the up-regulation of IL-10 has been reported by several earlier studies on tolerized human monocytes and murine macrophages (3,4,22,24,49), the up-regulation of the TRIF-specific gene IFN-␤ in endotoxin-tolerized cells was unexpected.…”

Section: Discussionmentioning

confidence: 82%

“…The involvement of NF-B and AP-1 in regulating LPS tolerance has been reported in the human monocytic cell line THP-1 (23). It is believed that tolerized monocytes/macrophages overexpress anti-inflammatory cytokines like IL-10 and TGF-␤, which can contribute to the suppression of proinflammatory cytokine expression in these cells (24,25). Finally, changes in the levels of negative regulators of the TLR pathway like MKP1, FLN29, ST2, and IRAK-M are also thought to contribute toward tolerance (26 -29), although the mechanism of their induction and their regulation are still poorly defined.…”

mentioning

confidence: 99%

Role for MyD88-Independent, TRIF Pathway in Lipid A/TLR4-Induced Endotoxin Tolerance

Biswas

Bist

Dhillon

et al. 2007

The Journal of Immunology

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Repeated exposure to low doses of endotoxin results in progressive hyporesponsiveness to subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance. In spite of its clinical significance in sepsis and characterization of the TLR4 signaling pathway as the principal endotoxin detection mechanism, the molecular determinants that induce tolerance remain obscure. We investigated the role of the TRIF/IFN-β pathway in TLR4-induced endotoxin tolerance. Lipid A-induced homotolerance was characterized by the down-regulation of MyD88-dependent proinflammatory cytokines TNF-α and CCL3, but up-regulation of TRIF-dependent cytokine IFN-β. This correlated with a molecular phenotype of defective NF-κB activation but a functional TRIF-dependent STAT1 signaling. Tolerance-induced suppression of TNF-α and CCL3 expression was significantly relieved by TRIF and IFN regulatory factor 3 deficiency, suggesting the involvement of the TRIF pathway in tolerance. Alternatively, selective activation of TRIF by poly(I:C)-induced tolerance to lipid A. Furthermore, pretreatment with rIFN-β also induced tolerance, whereas addition of IFN-β-neutralizing Ab during the tolerization partially alleviated tolerance to lipid A but not TLR2-induced endotoxin homo- or heterotolerance. Furthermore, IFNAR1−/− murine embryonal fibroblast and bone-marrow derived macrophages failed to induce tolerance. Together, these observations constitute evidence for a role of the TRIF/IFN-β pathway in the regulation of lipid A/TLR4-mediated endotoxin homotolerance.

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Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock

Abstract: Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-alpha release is downregulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.

Cited by 93 publications

References 26 publications

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Role for MyD88-Independent, TRIF Pathway in Lipid A/TLR4-Induced Endotoxin Tolerance

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