Effect of clarithromycin on rhinovirus-16 infection in A549 cells

Abstract

Clarithromycin (CM) has been found to inhibit the production of the intercellular adhesion molecule (ICAM)-1 and the secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects on the pathophysiological changes related to rhinovirus (RV) infection. The effect of CM on RV infection in A549 cells was therefore investigated.Cells were pre-treated with 1, 10 or 100 mM CM, either starting 3 days before infection and continuing thereafter, or by addition at the time of infection. RV titre, as measured by culture on Medical Research Council 5 cells, was reduced by CM, with the degree of reduction being greater when CM was added 3 days before infection than when it was added at the time of infection.CM treatment inhibited the RV-induced increase in ICAM-1 mRNA and protein, as well as the RVinduced secretion of IL-1b, IL-6, and IL-8. These effects were greater in cells treated with 10 mM than in those treated with 100 mM CM, and the maximum effect was observed 3 days after viral infection. In contrast, secretion of IL-8 was not inhibited significantly when CM was added at the time of viral infection.The findings of this study suggest that, in A549 cells, clarithromycin inhibits the induction of intercellular adhesion molecule-1 expression, cytokine elaboration, and viral infection.

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

“…In our study, we further demonstrated that azithromycin treatment had antiviral properties characterised by a seven-fold reduced RV1B replication in CF bronchial cells. Our findings confirm previous observations showing antiviral properties of macrolides such as azithromycin [12], erythromycin [10], clarithromycin [9] and bafilomycin A1 [11] in RV-infected airway epithelial cells. In addition, we observed that the decreased RV1B load after azithromycin treatment was not attributable to azithromycin-induced cytotoxicity.…”

“…cell adhesion molecule 1, which is the cell surface entry receptor for the major group of RVs, as a possible anti-RV mechanism of macrolide treatment [9][10][11]. Interestingly, this suggests that macrolides have antiviral effects on both minor-and major-type RV infection independently of the expression of the respective surface entry receptor.…”

“…Beyond their well-established antibacterial effects, a novel and potentially promising property of macrolides is the inhibition of respiratory viral infections in vitro in healthy airway epithelial cells [9][10][11][12]. Azithromycin potentially works by stimulating the host antiviral responses through the induction of interferons (IFNs) and IFN-stimulated genes (ISGs) [12].…”

Fosfomycin Suppresses Chemokine Induction in Airway Epithelial Cells Infected with Respiratory Syncytial Virus

“…Fourteen-membered-ring macrolides, such as erythromycin and clarithromycin, have been reported to reduce the titers of rhinovirus and influenza virus and the cytokine response induced by these viruses (14,31,33). Our results indicate that FOF modulates chemokine production via the suppression of NF-B activation independently of the replication of RSV (Fig.…”

“…The abilities of these antibiotics to inhibit the secretion of proinflammatory cytokines are thought to be mediated by inhibition of NF-B (3,13). Furthermore, pretreatment with erythromycin or clarithromycin has been reported to inhibit rhinovirus infection by suppressing the expression of virus receptors and reducing the rhinovirus-induced inflammatory cytokine response (14,31). Fosfomycin (FOF) is a structurally unique antibiotic that is chemically unrelated to any other known antimicrobial agent (16).…”