Pulmonary Manifestations of Systemic Disease: Mechanisms of Pulmonary Fibrosis |

Establishment of the Mouse Model of Acute Exacerbation of Idiopathic Pulmonary Fibrosis FREE TO VIEW

Yaru Wei, MD; Hui Qiu, MD; Qin Wu, MD; Yu-Kui Du, MD; Zhao-Fang Yin, MD; Shan-Shan Chen, MD; Yue-Ping Jin, MD; Meng-Meng Zhao, MD; Chen Wang, PhD; Dong Weng, PhD; Huiping Li, MD
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Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A453. doi:10.1016/j.chest.2016.02.472
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SESSION TITLE: Mechanisms of Pulmonary Fibrosis

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, April 17, 2016 at 09:45 AM - 11:15 AM

PURPOSE: To explore and establish an animal model of AE-IPF

METHODS: An animal model of idiopathic pulmonary fibrosis (IPF) was established using bleomycin (BLM). Then, BLM was administered a second time to induce AE-IPF (which mimics human AE-IPF), generating an animal model of AE-IPF. For comparison of AE-IPF in the new model vs. standard IPF, C57Bl/6 male mice were randomly divided into three groups: (1) the AE-IPF group: BLM was administered on day 0 and day 21; (2) the stable-IPF group: BLM was administered on day 0 and saline (NaCl) was administered on day 21; and (3) the control group: NaCl was administered on day 0 and day 21. Evaluation of the success of animal model was based on the survival of mice, including survival rate and changes in body weight, as well as assessment of pathological changes in lung tissue as determined using H&E staining and Masson’s trichrome staining for the observation of pulmonary inflammatory reactions and the degree of fibrosis. Preliminary investigation into the immunological mechanism of AE-IPF was also explored via the detection and identification of the inflammatory cells in mouse bronchoalveolar lavage fluid (BALF) and the concentrations of six cytokines (IL-4, IL-6, IL-10, IL-17A, MIG, and TGF-β1) in BALF supernatants, which were closely associated with IPF and AE-IPF

RESULTS: By week 4 after the second BLM administration, the mortality in the AE-IPF group was significantly greater (45%, 9/20) than that in the stable-IPF group (0/18) (p=0.0017). The average body weight in AE-IPF group were significantly lower than that in stable-IPF group (p<0.0001). In the AE-IPF group, inflammation and fibrosis were severer than that in stable-IPF group by histopathology analysis. In BALF, IL-17A, MIG (CXCL-9), IL-6 and TGF-β1 levels in AE-IPF group were significantly higher than that in stable-IPF group after second challenge of BLM. On day 24, the percentages of neutrophils and Th17 cells in BALF were significantly higher in AE-IPF group than in stable-IPF group (p=0.0034; p=0.0281); the percentage of neutrophils remained significantly higher in the AE-IPF group than in the stable-IPF group (p=0.0248) on day 28

CONCLUSIONS: A mouse model of AE-IPF can be successfully established using two administrations of BLM stimulations; Th17 cells may play a key role during the pathological process of AE-IPF

CLINICAL IMPLICATIONS: This model is suitable for the investigation of the pathogenesis of and intervention in AEIPF

DISCLOSURE: The following authors have nothing to disclose: Yaru Wei, Hui Qiu, Qin Wu, Yu-Kui Du, Zhao-Fang Yin, Shan-Shan Chen, Yue-Ping Jin, Meng-Meng Zhao, Chen Wang, Dong Weng, Huiping Li

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