Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion.
Słowa kluczowe
Abstrakcyjny
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.
CONCLUSIONS
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.
