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. 2020 May;43(5):526-539. doi: 10.1007/s12272-017-0950-x. Epub 2017 Aug 31.


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.

Keywords: Bronchial asthma; Clarithromycin; Cytokine; Nasal epithelial cell; Rhinovirus.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Cells, Cultured
  • Clarithromycin / pharmacology*
  • Cytokines / biosynthesis*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Interleukin-33 / antagonists & inhibitors
  • Interleukin-33 / biosynthesis
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / biosynthesis
  • Male
  • Middle Aged
  • Rhinovirus / drug effects*
  • Virus Replication / drug effects


  • Antiviral Agents
  • Cytokines
  • IL33 protein, human
  • IL6 protein, human
  • Interleukin-33
  • Interleukin-6
  • Interleukin-8
  • Clarithromycin