Implication of Interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD)

Cytokine. 2015 Aug;74(2):313-7. doi: 10.1016/j.cyto.2015.04.008. Epub 2015 Apr 25.


Interleukin (IL)-18 is a pro-inflammatory cytokine that was firstly described as an interferon (IFN)-γ-inducing factor. Similar to IL-1β, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. The platform for activating caspase-1 is known as the inflammasome, a multiple protein complex. Macrophages and dendritic cells are the primary sources for the release of active IL-18, whereas the inactive precursor remains in the intracellular compartment of mesenchymal cells. Finally, the IL-18 precursor is released from dying cells and processed extracellularly. IL-18 has crucial host defense and antitumor activities, and gene therapy to increase IL-18 levels in tissues protects experimental animals from infection and tumor growth and metastasis. Moreover, multiple studies in experimental animal models have shown that IL-18 over-expression results to emphysematous lesions in mice. The published data prompt to the hypothesis that IL-18 induces a broad spectrum of COPD-like inflammatory and remodeling responses in the murine lung and also induces a mixed type 1, type 2, and type 17 cytokine responses. The majority of studies identify IL-18 as a potential target for future COPD therapeutics to limit both the destructive and remodeling processes occurring in COPD lungs.

Keywords: Chronic obstructive pulmonary disease; Inflammasome; Interleukin (IL)-18.

Publication types

  • Review

MeSH terms

  • Animals
  • Caspase 1 / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Humans
  • Interleukin-18 / immunology*
  • Lung / immunology*
  • Lung / pathology
  • Macrophages / immunology*
  • Macrophages / pathology
  • Mice
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / therapy
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology


  • IL18 protein, human
  • Interleukin-18
  • Caspase 1