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Interleukin-18, a proinflammatory cytokine.

C A Dinarello1

  • 1University of Colorado Health Sciences Center, Denver 80262, USA.

European Cytokine Network
|February 24, 2001
PubMed
Summary
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Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in various diseases. Neutralizing IL-18 offers therapeutic potential by reducing disease severity and enhancing host defense mechanisms.

Area of Science:

  • Immunology
  • Cytokine Biology
  • Inflammation Research

Background:

  • Interleukin-18 (IL-18) is recognized as a proinflammatory cytokine that induces interferon-gamma (IFN-γ) and T helper 1 (Th1) responses.
  • Antibodies neutralizing endogenous IL-18 have demonstrated efficacy in reducing disease severity across multiple animal models.
  • IL-18 neutralization prevents endotoxin lethality and prolongs survival, even in models where interferon-gamma is not the primary mediator.

Discussion:

  • Anti-IL-18 antibodies protect the liver from toxin-induced or T cell-mediated cellular injury.
  • In hepatic melanoma metastasis models, IL-18 blockade inhibits malignant cell adherence by downregulating vascular endothelial adhesion molecule-1 expression.
  • IL-18 synergizes with IL-12 to stimulate IFN-γ production by T cells and natural killer cells; however, IL-18 neutralization blocks this IL-12-induced IFN-γ production.

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Key Insights:

  • The proinflammatory actions of IL-18 are crucial for its role in enhancing host defense against tumors, often mediated through IFN-γ.
  • Neutralization of IL-18 in models of arthritis, lung injury, and inflammatory bowel disease highlights its significant role in mediating inflammatory processes.
  • IL-18 blockade demonstrates therapeutic benefits in diverse inflammatory conditions and cancer metastasis models.

Outlook:

  • Further research into IL-18's dual role in host defense and inflammation may uncover novel therapeutic strategies.
  • Targeting IL-18 could offer a promising approach for managing autoimmune diseases and inflammatory disorders.
  • Investigating the precise mechanisms underlying IL-18's contribution to tumor immunity and metastasis is warranted.