Allergy and Airway: Asthma III |

Intranasal Administration of IL-27 Pre-OVA Sensitization Alleviate Allergic Airway Inflammation in Mice Model FREE TO VIEW

Zhihong Chen, MD; Xiaoqiong Su, MA; Nian Dong, MA; Kan Xu, MA; Xiangdong Wang, MD
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Zhongshan Hospital, Shanghai, China

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

Chest. 2016;149(4_S):A29. doi:10.1016/j.chest.2016.02.031
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: IL-27 is a family member of Th1 type cytokines, which could promote Th1 development and inhibit Th2 and Th17 development as well. Asthma is Th2-prone chronic airway inflammation. In this study, animal models were set up to observe whether IL-27 intervention could diminish allergic airway inflammation and to investigate the related molecular mechanisms.

METHODS: Two IL-27 intervention ways were set up, one of which is low-dose-multiple preventive model, the other is high-dose-few times treating model. Airway hyperresponsiveness BAL, HE staining were tested. The mRNA, protein level of STAT1 and GADD45γ were measured through qPCR and western blot.

RESULTS: In asthma model, both STAT1 phosphorylation and GADD45γ expression which mediate IFN-r producing in the end were verified to be impaired by qPCR and Western blot, due to OVA induced inflammation. IL-27 administration by nasal pre-OVA sensitization could reverse GADD45γ impairment but not STAT1 phosphorylation. So, In low-dose-multiple prevention group, IL-27 inhibits inflammation around bronchial and vascular obviously. In the other hand, IL-27 has little effect on alleviating airway inflammation when used post-OVA sensitization because of already committed Th2 cell resident in the airway.

CONCLUSIONS: Our model demonstrated IL-27 resistance when used post-OVA sensitization due to existed Th2- induced STAT1 and GADD45γ downregulation. Low-dose-multiple preventive way improve airway inflammation greatly by reversing GADD45γ expression but not STAT1-Py which indicate intervention time-point is critically important in modulating Th1-Th2 balance when using cytokine strategies.

CLINICAL IMPLICATIONS: 1. Cytokine strategy might be a potential way to regulate Th1-Th2 unbalance in asthma. 2. The intervention time point of cytokine will be critical when using this method in vivo.

DISCLOSURE: The following authors have nothing to disclose: Zhihong Chen, Xiaoqiong Su, Nian Dong, Kan Xu, Xiangdong Wang

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