| First Author | Hoshino T | Year | 2007 |
| Journal | Am J Respir Crit Care Med | Volume | 176 |
| Issue | 1 | Pages | 49-62 |
| PubMed ID | 17400729 | Mgi Jnum | J:147547 |
| Mgi Id | MGI:3841361 | Doi | 10.1164/rccm.200603-316OC |
| Citation | Hoshino T, et al. (2007) Pulmonary inflammation and emphysema: role of the cytokines IL-18 and IL-13. Am J Respir Crit Care Med 176(1):49-62 |
| abstractText | 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. |
