Effect of Clarithromycin on Rhinovirus-16 Infection in A549 Cells

ABSTRACT

BACKGROUND AND OBJECTIVES: Rhinovirus enters into airway epithelial cells via the membrane bound receptor ICAM-1. Infected epithelial cells secrete the cytokines such as IL-6 and IL-8, which induce neutrophil migration into the epithelium. Clarithromycin has been found to inhibit ICAM-1 production and secretion of IL-6 and IL-8. We hypothesized that these properties of clarithromycin may be applicable in treating rhinovirus infection. MATERIALS AND METHOD: We assayed the effects of clarithromycin on rhinovirus infected A549 cells. ICAM-1 expression was assessed by flow cytometry, and cytokine secretion was assayed by ELISA. The level of viral replication was expressed as viral titer, which was determined through viral culture on MRC-5 cells. RESULTS: The mean fluorescence intensity of ICAM-1 in rhinovirus infected cells decreased from 12.4+/-0.59 to 9.2+/-0.72 after treatment with clarithromycin. The production of IL-1beta, IL-6, and IL-8 was decreased after rhinovirus infected cells were treated with clarithromycin. In the absence of rhinovirus infection, clarithromycin had no effect on ICAM-1 expression or cytokine secretion. The rhinovirus titer in infected cells was 10(3.71) TCID 50 U/ml, which was reduced following clarithromycin treatment to 10(2.14) TCID 50 U/ml. CONCLUSION: These findings suggest that clarithromycin treatment of rhinovirus infected A549 cells inhibited rhinovirus induction of increased ICAM-1 expression, cytokine elaboration, and viral replication.