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.


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.
Cho
J Y
JY
Department of Medicine, University of California, San Diego, La Jolla 92093-0635, USA.
Miller
M
M
Baek
K J
KJ
Castaneda
D
D
Nayar
J
J
Roman
M
M
Raz
E
E
Broide
D H
DH
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001991:Bronchitis / Q000188:drug therapy* / Q000821:virology; D016085:Bronchoconstrictor Agents; D002460:Cell Line; D004247:DNA / Q000627:therapeutic use*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007372:Interferons / Q000494:pharmacology; D018793:Interleukin-13 / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism / Q000821:virology; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000254:growth & development / Q000302:isolation & purification; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016085:Bronchoconstrictor Agents; D018793:Interleukin-13; D016210:Methacholine Chloride; D007371:Interferon-gamma; D004247:DNA; D007372:Interferons