Which inflammatory mediators are involved in the pathogenesis of sepsis?

Updated: Oct 07, 2020
  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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Answer

The evidence that sepsis results from an exaggerated systemic inflammatory response induced by infecting organisms is compelling. Inflammatory mediators are the key players in the pathogenesis of sepsis (see Table 3 below).

Table 3. Mediators of Sepsis (Open Table in a new window)

Type

Mediator

Activity

Cellular mediators

LPS

Activation of macrophages, neutrophils, platelets, and endothelium releases various cytokines and other mediators

Lipoteichoic acid

Peptidoglycan

Superantigens

Endotoxin

Humoral mediators

Cytokines

Activate inflammatory pathways

  • TNF-α and IL-1β

Potent proinflammatory effect

  • IL-6

Acts as pyrogen, stimulates B- and T-cell proliferation

  • IL-8

Neutrophil chemotactic factor, activation and degranulation of neutrophils

  • IL-10

Inhibits cytokine production, induces immunosuppression

  • MIF

Activates macrophages and T cells

  • G-CSF

Promotes neutrophil and macrophage, platelet activation

Complement

Promotes neutrophil and macrophage, platelet activation and chemotaxis, other proinflammatory effects

Nitric oxide

Involved in hemodynamic alterations of septic shock; cytotoxic, augments vascular permeability, contributes to shock

 

Lipid mediators

Enhance vascular permeability and contribute to lung injury

 

  • Phospholipase A2

 

 

  • PAF

 

 

  • Eicosanoids

 

 

Arachidonic acid metabolites

Augment vascular permeability

 

Adhesion molecules

Enhance neutrophil-endothelial cell interaction, regulate leukocyte migration and adhesion, and play a role in pathogenesis of sepsis; increased levels of VAP-1 activity and anchor protein SDC-1 content have been found in critically ill patients with septic shock [12]

 

  • Selectins

 

 

  • Leukocyte integrins

 

 

  • High mobility box–1

Late mediator of endotoxin-induced lethality and tissue repair

 

G-CSF = granulocyte colony-stimulating factor; IL = interleukin; LPS = lipopolysaccharide; MIF = macrophage inhibitory factor; PAF = platelet-activating factor; SDC-1 = syndecan-1; TNF = tumor necrosis factor; VAP-1 = vascular adhesion protein–1.

Source:  Cinel I, Opal SM. Molecular biology of inflammation and sepsis: a primer. Crit Care Med. 2009 Jan;37(1):291-304. [13]

 

 


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