Published ahead of print on March 30, 2007, doi:10.1164/rccm.200603-316OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200603-316OC
Pulmonary Inflammation and EmphysemaRole of the Cytokines IL-18 and IL-131 Department of Internal Medicine 1, and 2 Pathology, Kurume University School of Medicine, Kurume, Japan; 3 Laboratory of Experimental Immunology, National Cancer Institute, Center for Cancer Research, Frederick, Maryland; 4 Internal Medicine 3, and Cardiovascular Research Institute, and 5 Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, Japan; 6 Division of Pathology and Cell Biology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan Correspondence and requests for reprints should be addressed to Tomoaki Hoshino, M.D., Ph.D., Department of Internal Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830–0011, Japan. E-mail: hoshino{at}med.kurume-u.ac.jp 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- Conclusions: Our results indicate that IL-18 and IL-13 may have an important role in the pathogenesis of COPD.
Key Words: emphysema • IFN-
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, 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-
