Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion

Background: Immunostimulatory DNA sequences (ISS) activate the innate immune system to generate antiviral cytokines, such as IFN-gamma. Objective: This study investigated whether ISS could reduce viral load, mucus secretion, airway inflammation, and airway hyperreactivity to methacholine in a mouse model of respiratory syncytial virus (RSV) infection. Methods: Mice were pretreated with ISS 6 days before RSV infection, and lung indices of RSV viral load (viral titer and PCR), bronchoalveolar lavage fluid cytokines (IFN-gamma), airway inflammation (peribronchial inflammation and periodic acid-Schiff-positive mucus cells), and airway hyperreactivity (methacholine responsiveness) were assessed 4 to 6 days after RSV infection. Results: ISS induced the expression of the antiviral cytokine IFN-gamma in the lung, and this was associated with significantly reduced RSV viral titers, mucus secretion, and peribronchial inflammation. ISS reduced, but did not significantly inhibit, RSV-induced airway hyperreactivity to methacholine. Conclusion: Because ISS induced significant levels of lung IFN-gamma, an immunization strategy based solely on the administration of IFN-gamma may be insufficient to inhibit RSV-induced airway hyperreactivity to methacholine, an endpoint important in the subset of RSV-infected subjects with asthma.