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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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)




Cellular mediators


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

Lipoteichoic acid




Humoral mediators


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


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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