Levofloxacin Inhibits Rhinovirus Infection in Primary Cultures of Human Tracheal Epithelial Cells

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Respiratory virus infections, including infections with rhinoviruses (RVs), are related to exacerbations of chronic obstructive pulmonary disease (COPD). A new quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial infections that cause COPD exacerbations as well as bacterial infections that are secondary to viral infection in COPD patients. However, the inhibitory effects of LVFX on RV infection and RV infection-induced airway inflammation have not been studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX pretreatment reduced the RV14 titer, the level of cytokines in the supernatant, the amount of RV14 RNA in the cells after RV14 infection, and the cells' susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and the concentration of the soluble form of ICAM-1 in the supernatant before RV14 infection. LVFX pretreatment also decreased the number and the fluorescence intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX pretreatment inhibited the activation of nuclear factor κB proteins, including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human RV). These results suggest that LVFX inhibits major-group rhinovirus infections in part by reducing ICAM-1 expression levels and the number of acidic endosomes. LVFX may also modulate airway inflammation in rhinoviral infections.</jats:p>

Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury

“…Our immunohistochemical findings show this activation to occur in isolated cells that could correspond to infiltrating leukocytes, although the lack of double immunostaining precludes any firm conclusion. It has been reported that both macrolides [28] and quinolones [29] may block NFκB activation, resembling our own results. However, we did not find any differences in Cxcl2 expression that could explain the decreased neutrophilic infiltrates in animals receiving clarithromycin.…”

Update on Human Rhinovirus and Coronavirus Infections

“…Recently, levofloxacin has been found to inhibit HRV infection in primary cell cultures employing human tracheal epithelial cells. 188 Levofloxacin pretreatment decreased mRNA levels of ICAM-1. Macrolides have also been reported to reduce ICAM-1 expression and HRV-induced cytokines in vitro and in vivo.…”

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

“…Furthermore, fluoroquinolones have been shown to suppress hepatitis C virus (HCV, family Flaviviridae) replication in vitro, possibly by inhibiting the viral helicase [32], but this suppression has not translated into an effective treatment for patients with liver failure due to chronic HCV infection [33]. Additionally, fluoroquinolones suppress rhinovirus infection by reducing expression of the viral receptor on cells [34]. Recently, Xu et al demonstrated that a high concentration of enoxacin administered to human neuronal progenitor cells (hNPC) and brain organoids prior to and after infection with ZIKV suppressed viral replication and restored normal cellular proliferation, possibly by enhancing RNAi [35].…”