Respiratory Syncytial Virus Infections Augment Airway Reactivity in Mice Exposed to Chlorine (Cl2)

Abstract

Chlorine (Cl2) gas inhalation causes respiratory system injury including epithelial cell sloughing, edema and airway hyperreactivity, leading to reactive airway dysfunction syndrome (RADS), a prelude to asthma. However, little is known about how pre‐existing infections alter the responses of animals to a subsequent Cl2 exposure. Herein Balb/c mice were infected with respiratory syncytial virus (RSV), a common respiratory infection in children, via intranasal instillation of 100 microliters of RSV A2 (106 PFU/ml) or vehicle. Four days later they were exposed to 187 ppm Cl2 for 30 minutes in environmental chambers and returned to room air. Measurements of airway resistance and elastance, prior to and following challenge with aerosolized methacholine (up to 50 mg/ml) were conducted in anesthetized mice with a flexiVent, 24 h post exposure. RSV infection greatly increased: (1) airway resistance and elastance after methacholine challenge in Cl2 exposed mice as compared to vehicle infected mice; (2) levels of IL‐10, interferon‐γ and RANTES and (3) levels of low molecular weight hyaluronan and inter‐α‐trypsin inhibitor (IaI; a factor necessary for the binding of hyaluronan to its receptor) in the BAL. Hyaluronan has been shown to contribute to airway hyperresponsiveness in mice exposed to ozone. We concluded that pre‐existing viral infections increase the susceptibility of mice to Cl2 induced airway injury via the upregulation of a variety of inflammatory cytokines and hyaluronan.