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

Abstract

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.

• Authors: Tomoaki Hoshino, Seiya Kato, Naoki Oka, Haruki Imaoka, Takashi Kinoshita, Satoko Takei, Yasuhiko Kitasato, Tomotaka Kawayama, Tsutomu Imaizumi, Kentaro Yamada, Howard A Young, Hisamichi Aizawa
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 176 Issue 1 Pg. 49-62 (Jul 01 2007) ISSN: 1535-4970 [Electronic] United States
• PMID: 17400729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-13
• Interleukin-18

Topics

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