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

• Published in: Journal of allergy and clinical immunology Vol. 108; no. 5; pp. 697 - 702
• Main Authors: Cho, Jae Youn, Miller, Marina, Baek, Kwang Je, Castaneda, Diego, Nayar, Jyothi, Roman, Mark, Raz, Eyal, Broide, David H.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.11.2001; Elsevier
• Subjects: Adjuvants, Immunologic - therapeutic use; Allergic diseases; Animals; Asthma - drug therapy; Asthma - metabolism; Asthma - virology; Biological and medical sciences; Bronchial Hyperreactivity - diagnosis; Bronchitis - drug therapy; Bronchitis - virology; Bronchoconstrictor Agents; Cell Line; Chronic obstructive pulmonary disease, asthma; DNA - therapeutic use; Female; IFN-γ, asthma; Immunopathology; Immunostimulatory DNA sequence; Interferon-gamma - biosynthesis; Interferons - pharmacology; Interleukin-13 - biosynthesis; Lung - metabolism; Lung - virology; Medical sciences; methacholine; Methacholine Chloride; Mice; Mice, Inbred BALB C; Mucus - secretion; Pneumology; Respiratory and ent allergic diseases; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - drug therapy; Respiratory Syncytial Virus Infections - metabolism; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Viruses - growth & development; Respiratory Syncytial Viruses - isolation & purification; Viral Load; Virus Replication - drug effects; PAS; RSV; ISS; Penh; Immunostimulatory DNA sequence; M-ODN; respiratory syncytial virus; BAL; NK; IFN-γ, asthma; Animal model; Hyperreactivity; Spumavirinae; Prevention; Respiratory tract; Complication; Obstructive pulmonary disease; Mechanism of action; Aminoacid sequence; Immunostimulation; Respiratory disease; Rodentia; Retroviridae; Inflammation; Asthma; Infection; Virus; Vertebrata; Mammalia; Human syncytial virus; Mouse; Animal; DNA; Viral disease; Gamma interferon
• ISSN: 0091-6749
• DOI: 10.1067/mai.2001.119918

Background: Immunostimulatory DNA sequences (ISS) activate the innate immune system to generate antiviral cytokines, such as IFN-γ. 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-γ), 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-γ 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-γ, an immunization strategy based solely on the administration of IFN-γ may be insufficient to inhibit RSV-induced airway hyperreactivity to methacholine, an endpoint important in the subset of RSV-infected subjects with asthma. (J Allergy Clin Immunol 2001;108:697-702.)