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EcoSal Plus

Domain 8:

Pathogenesis

Cytokines and Sepsis

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  • Authors: Chloé Kaech1, Pierre-Yves Bochud2, and Thierry Calandra3
  • Editor: Michael S. Donnenberg4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland; 2: Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; 3: Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland; 4: University of Maryland, School of Medicine, Baltimore, MD
  • Received 15 March 2006 Accepted 12 June 2006 Published 01 September 2006
  • Address correspondence to Thierry Calandra Thierry.Calandra@chuv.ch
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  • Abstract:

    This review reviews the critical role played by cytokines in the pathogenesis of sepsis. It focuses on prototypic pro-inflammatory and anti-inflammatory cytokines and their influence on mortality in experimental animal models of endotoxemia and of live sepsis. The review reviews the results of clinical trials on anticytokine therapy in patients with severe sepsis or septic shock. The recognition of the critical role played by tumor necrosis factor (TNF), a secreted 17kDa cytokine, in endotoxic and gram-negative shock has been a major step forward in our understanding of the pathogenesis of sepsis. The review describes the role of TNF, IL1, and IL6 in animal models of endotoxemia and sepsis. Given the pivotal role played by TNF in experimental sepsis and the fact that elevated concentrations of TNF were detected in the circulation of patients with sepsis, anti-TNF treatment strategies were investigated as adjunctive therapy for severe sepsis and septic shock. Several studies demonstrated that high levels of interleukin-6 (IL-6) are associated with an increased risk for fatal outcome. Gamma interferon (IFN-γ), IL-12, and IL-18 are functionally related cytokines. A recent study has indicated that transgenic mice overexpressing IL-15 are resistant to an otherwise lethal intraperitoneal challenge. IL4, IL10, and IL13are prototypic anti-inflammatory cytokines. Their classification as anti-inflammatory cytokines is based on the observation that these molecules inhibit the production of proinflammatory cytokines (primarily TNF and IL1) and toxic oxygen and reactive nitrogen species by myeloid cells.

  • Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15

Key Concept Ranking

Major Histocompatibility Complex
0.50526696
Tumor Necrosis Factor
0.5030203
Mitogen-Activated Protein Kinase Pathway
0.47353438
0.50526696

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ecosalplus.8.8.15.citations
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/content/journal/ecosalplus/10.1128/ecosalplus.8.8.15
2006-09-01
2017-03-29

Abstract:

This review reviews the critical role played by cytokines in the pathogenesis of sepsis. It focuses on prototypic pro-inflammatory and anti-inflammatory cytokines and their influence on mortality in experimental animal models of endotoxemia and of live sepsis. The review reviews the results of clinical trials on anticytokine therapy in patients with severe sepsis or septic shock. The recognition of the critical role played by tumor necrosis factor (TNF), a secreted 17kDa cytokine, in endotoxic and gram-negative shock has been a major step forward in our understanding of the pathogenesis of sepsis. The review describes the role of TNF, IL1, and IL6 in animal models of endotoxemia and sepsis. Given the pivotal role played by TNF in experimental sepsis and the fact that elevated concentrations of TNF were detected in the circulation of patients with sepsis, anti-TNF treatment strategies were investigated as adjunctive therapy for severe sepsis and septic shock. Several studies demonstrated that high levels of interleukin-6 (IL-6) are associated with an increased risk for fatal outcome. Gamma interferon (IFN-γ), IL-12, and IL-18 are functionally related cytokines. A recent study has indicated that transgenic mice overexpressing IL-15 are resistant to an otherwise lethal intraperitoneal challenge. IL4, IL10, and IL13are prototypic anti-inflammatory cytokines. Their classification as anti-inflammatory cytokines is based on the observation that these molecules inhibit the production of proinflammatory cytokines (primarily TNF and IL1) and toxic oxygen and reactive nitrogen species by myeloid cells.

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Figures

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Figure 1

+, beneficial effects; −, detrimental effects; MAMP, microbe-associated molecular patterns; MRR, microbial recognition receptors.

Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15
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Tables

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Table 1

Microorganisms most frequently isolated from patients with severe sepsis and septic shock

Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15
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Table 2

Evaluation of the role of TNF, IL-1, and IL-6 in animal models of endotoxemia and sepsis

Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15
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Table 3

Clinical trials of anticytokine therapies for patients with severe sepsis or septic shock

Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15
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Table 4

Evaluation of the role of IFN-γ, IL-12, IL-15, IL-18, MIF, and HMG-1 in animal models of endotoxemia and sepsis

Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15
Generic image for table
Table 5

Evaluation of the role of IL-4, IL-10, IL-13, and TGF-β1 in animal models of endotoxemia and sepsis

Citation: Kaech C, Bochud P, Calandra T. 2006. Cytokines and Sepsis, EcoSal Plus 2006; doi:10.1128/ecosalplus.8.8.15

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