Long-term azithromycin ameliorates not only airway inflammation but also remodeling in a murine model of chronic asthma

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• 作者：Ji Young Kang ; Mi Ran Jo ; Hyeon Hui Kang ; Sung Kyoung Kim ; Myoung Sook Kim ; Yong Hyun Kim ; Seok Chan Kim ; Soon Seog Kwon ; Sook Young Lee ; Jin Woo Kim ; ^{medkjw@catholic.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Asthma ; Airway remodeling ; Azithromycin ; Macrolide
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：36
• 期：Complete
• 页码：37-45
• 全文大小：2262 K

文摘

We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling.

Methods

Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated.

Results

Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group.

Conclusions

This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.