What is the role of cytokines in the pathophysiology 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

An initial step in the activation of innate immunity is the de novo synthesis of small polypeptides (cytokines) that induce protean manifestations on most cell types, from immune effector cells to vascular smooth muscle and parenchymal cells. Several cytokines are induced, including tumor necrosis factor (TNF) and interleukins (ILs), especially IL-1. These factors help keep infections localized; however, once the infection progresses, the effects can also be detrimental.

Circulating levels of IL-6 correlate have a strong correlation with outcome. High levels of IL-6 are associated with mortality, but the role of this cytokine in pathogenesis is not clear. IL-8 is an important regulator of neutrophil function, synthesized and released in significant amounts during sepsis. IL-8 contributes to the lung injury and dysfunction of other organs.

Chemokines (eg, monocyte chemoattractant protein [MCP]-1) orchestrate the migration of leukocytes during endotoxemia and sepsis. Other cytokines thought to play a role in sepsis include the following:

  • IL-10

  • Interferon gamma

  • IL-12

  • Macrophage migration inhibition factor (MIF or MMIF)

  • Granulocyte colony-stimulating factor (G-CSF)

  • Granulocyte macrophage colony-stimulating factor (GM-CSF)

In addition, cytokines activate the coagulation pathway, resulting in capillary microthrombi and end-organ ischemia. [14, 15, 16] (See Abnormalities of coagulation and fibrinolysis, below.)


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