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Clarithromycin decreases rhinovirus replication and cytokine production in nasal epithelial cells from subjects with bronchial asthma: effects on IL-6, IL-8 and IL-33

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Abstract

Rhinoviral infection is associated with an increased risk of asthma attacks. The macrolide clarithromycin decreases cytokine production in nasopharyngeal aspirates from patients with wheezing, but the effects of macrolides on cytokine production in nasal epithelial cells obtained from asthmatic subjects remain unclear. Here, human nasal epithelial cells were infected with type-14 rhinovirus (RV14), a major RV group. Titers and RNA of RV14 and cytokine concentrations, including IL-1β and IL-6, were higher in the supernatants of the cells obtained from subjects with bronchial asthma (asthmatic group) than in those from the non-asthmatic group. Pretreatment with clarithromycin decreased RV14 titers, viral RNA and cytokine concentrations, and susceptibility to RV14 infection. Pretreatment with clarithromycin also decreased IL-33 production, which was detected after infection. Pretreatment with clarithromycin decreased the expression of intercellular adhesion molecule-1, the receptor for RV14, after infection, the number and fluorescence intensity of the acidic endosomes through which RV RNA enters the cytoplasm, and the activation of nuclear factor kappa-B proteins in nuclear extracts. These findings suggested that RV replication and cytokine production may be enhanced in nasal epithelial cells obtained from subjects with bronchial asthma and may be modulated by clarithromycin.

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Acknowledgements

We thank Biomedical Research Unit of Tohoku University Hospital for technical support. Dr. Yamaya is a Professor in the Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine. This department was funded by eight pharmaceutical companies, which are as follows: Kyorin Pharmaceutical Co. Ltd., Mylan EPD, LLC., Taisho Toyama Pharmaceutical Co., Ltd., Toyama Chemical Co., Ltd., Nippon Boehringer-Ingelheim Co., Ltd., Teijin Pharma Co., Ltd., and AstraZeneca Co. Ltd. and Otsuka Pharmaceutical Co. Ltd.

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Authors and Affiliations

  1. Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Mutsuo Yamaya, Xue Deng & Nadine Lusamba Kalonji

  2. Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan

    Kazuhiro Nomura & Kazuya Arakawa

  3. Department of Otolaryngology, Tohoku Kosai Hospital, Sendai, 980-0803, Japan

    Mitsuru Sugawara

  4. Virus Research Center, Clinical Research Division, Sendai National Hospital, Sendai, 983-8520, Japan

    Hidekazu Nishimura

  5. Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan

    Mitsuhiro Yamada

  6. Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan

    Ryoichi Nagatomi

  7. Laboratory of Rehabilitative Auditory Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, 980-8575, Japan

    Tetsuaki Kawase

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  1. Mutsuo Yamaya
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  2. Kazuhiro Nomura
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Correspondence to Mutsuo Yamaya.

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Yamaya, M., Nomura, K., Arakawa, K. et al. Clarithromycin decreases rhinovirus replication and cytokine production in nasal epithelial cells from subjects with bronchial asthma: effects on IL-6, IL-8 and IL-33. Arch. Pharm. Res. 43, 526–539 (2020). https://doi.org/10.1007/s12272-017-0950-x

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