Obstructive Lung Diseases: COPD: Etiology |

Inhibitory Effects of Corticosteroids on the Smoke-Induced Pulmonary Inflammation is Potentiated by Concomitant Administration of Pentoxifylline or Roflumilast FREE TO VIEW

Dandan Chen, MMed; Luxi Zhou, PhD; Changzhi Zhou, MMed; Ping Wu, PhD; Jinnong Zhang, PhD
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WuHan Union Hospital, Tongji Medical College, Huazhong University of Science and Technololgy, Wuhan, China

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

Chest. 2016;149(4_S):A356. doi:10.1016/j.chest.2016.02.371
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SESSION TYPE: Original Investigation Poster

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

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a disease of inflammation that is commonly induced by chronic exposure of cigarettes smoke. Unlike bronchial asthma, the pulmonary inflammation is insensitive to corticosteroids. The purpose of this study is to investigate if addition of pentoxifylline (PTX) or roflumilast (ROF), the anti-inflammatory effects of corticosteroids would be restored or potentiated.

METHODS: Male C57BL/6 mice were randomized into smoke exposure (CS), CS with dexamethasone (DEX), or with ROF, or with PTX, or with both DEX and ROF, or with both DEX and PTX, respectively, for 24 weeks. The morphology of the lungs, the levels of TNF-α and IL-8 in bronchoalveolar lavage fluid (BALF), the expression of reactive oxygen species (ROS) in lung parenchyma, the activities of phosphorylated protein kinase B (pAkt) and histone deacetylase 2 (HDAC2) in lung homogenates were measured accordingly.

RESULTS: CS increased the levels of TNF-α and IL-8 as well as the expressions of ROS and pAkt, but decreased HDAC2 activity (P <0.05 for all comparisons), which was associated with an augmentation of lung inflammation. DEX, PTX or ROF alone decreased the levels of TNF-α and IL-8 as well as the expressions of ROS and pAkt, increased the HDAC2 activity (P <0.05 for all comparisons), while concomitant administration of DEX and PTX or ROF, more obvious expression of HDAC2 was noted (P <0.05), which was consistent with a more overt reduction of pAkt expression (P <0.05), particularly in the combination of DEX and PTX.

CONCLUSIONS: The anti-inflammatory effect of corticosteroid on lung inflammation induced by CS could be potentiated by addition of PTX or ROS, which was associated with augmentation of HDAC2 activity, and consistently, the anti-inflammatory effect was increased.

CLINICAL IMPLICATIONS: The HDAC2 activity could be augmented significantly by the concomitant administration of DEX and PTX or ROF, implies that the combination of corticosteroid with phosphodiesterases inhibitors, such as PTX or ROF may be a new approach for the effective treatment of COPD.

DISCLOSURE: The following authors have nothing to disclose: Dandan Chen, Luxi Zhou, Changzhi Zhou, Ping Wu, Jinnong Zhang

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