Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view

Wibke Schulte, Jürgen Bernhagen, Richard Bucala, Wibke Schulte, Jürgen Bernhagen, Richard Bucala

Abstract

Sepsis and septic shock are among the leading causes of death in intensive care units worldwide. Numerous studies on their pathophysiology have revealed an imbalance in the inflammatory network leading to tissue damage, organ failure, and ultimately, death. Cytokines are important pleiotropic regulators of the immune response, which have a crucial role in the complex pathophysiology underlying sepsis. They have both pro- and anti-inflammatory functions and are capable of coordinating effective defense mechanisms against invading pathogens. On the other hand, cytokines may dysregulate the immune response and promote tissue-damaging inflammation. In this review, we address the current knowledge of the actions of pro- and anti-inflammatory cytokines in sepsis pathophysiology as well as how these cytokines and other important immunomodulating agents may be therapeutically targeted to improve the clinical outcome of sepsis.

Figures

Figure 1
Figure 1
Initiation of the immune response following infection. Immune cells of the innate immune system recognize invading pathogens via Toll-like receptors (TLRs). The binding of pathogen-associated molecular patterns (PAMPs), such as peptidoglycan, lipopolysaccharide (LPS), or flagellin, to TLRs initiates signal transduction cascades that lead to the activation of nuclear factor κB (NF-κB). NF-κB is subsequently translocated into the nucleus where it induces the expression of cytokines and chemokines.

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