Pulmonary inflammation and emphysema: role of the cytokines IL-18 and IL-13

Am J Respir Crit Care Med. 2007 Jul 1;176(1):49-62. doi: 10.1164/rccm.200603-316OC. Epub 2007 Mar 30.


Rationale: Chronic obstructive pulmonary disease (COPD) is believed to be an inflammatory cytokine-driven disease, but a causal basis that can be associated with a specific cytokine has not been directly demonstrated. We have previously reported that proinflammatory cytokine IL-18 expression is important in the pathogenesis of pulmonary inflammation and lung injury in mice. Our results demonstrate that IL-18 overproduction in the lungs can induce lung diseases, such as pulmonary inflammation, lung fibrosis, and COPD.

Objectives: We analyzed the role of IL-18 in the pathogenesis of COPD.

Methods: Using the human surfactant protein C promoter to drive expression of mature mouse IL-18 cDNA, we developed two different lines of transgenic (Tg) mice that overproduced mouse mature IL-18 in the lungs either constitutively or in response to doxycycline.

Measurements and main results: Constitutive overproduction of IL-18 in the lungs resulted in the increased production of IFN-gamma, IL-5, and IL-13, and chronic pulmonary lung inflammation with the appearance of CD8+ T cells, macrophages, neutrophils, and eosinophils. Increased lung volume, severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension were observed in (more than 15-wk-old) Tg mice. Interestingly, disruption of the IL-13 gene, but not the IFN-gamma gene, prevented emphysema and pulmonary inflammation in Tg mice. Moreover, when IL-18 production was induced in lung tissues for 4 weeks through the use of a doxycycline-dependent surfactant protein C promoter, interstitial inflammation was induced.

Conclusions: Our results indicate that IL-18 and IL-13 may have an important role in the pathogenesis of COPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Emphysema / immunology*
  • Emphysema / pathology
  • Emphysema / physiopathology*
  • Interleukin-13 / immunology*
  • Interleukin-18 / immunology*
  • Interleukin-18 / metabolism
  • Mice
  • Mice, Transgenic
  • Pneumonia / immunology
  • Pneumonia / pathology
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / pathology
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology


  • Interleukin-13
  • Interleukin-18