Persistence of airway hyperresponsiveness and viral antigen following respiratory syncytial virus bronchiolitis in young guinea-pigs.
Respiratory syncytial virus (RSV) bronchiolitis in infancy is known to be followed by chronic respiratory symptoms and airway hyperresponsiveness in a subgroup of patients. To further investigate the pathogenesis of RSV-induced chronic airway pathology, we infected young guinea-pigs at 4 weeks of age with RSV applied as an aerosol (n=30), and control guinea-pigs with virus-free culture medium (n=24). Infection was confirmed by positive antibody titre to RSV after 6 weeks, and by typical pathological changes of bronchiolitis after 1 week in six animals from each group. Airway hyperresponsiveness was measured weekly for 5 weeks by histamine challenge, using body-plethysmographic measurement of compressed air (CA). The provocative concentration of histamine producing significant airway obstruction (i.e. CA = 0.1 mL) (PC0.1 mL CA in mg x mL(-1)) was calculated from dose-response curves. Six weeks postinfection, the lungs were investigated for the presence of inflammation and of viral antigen by immunofluorescence and immunohistochemistry using a rabbit hyperimmune serum and monoclonal antibodies. Airway responsiveness was increased in the RSV group 1 week postinfection compared to the control group (PC0.1 mL CA median 2.50 vs >10 mg x mL(-1); p<0.001) and this persisted up to 5 weeks postinfection (PC0.1 mL CA median 1.61 vs >10 mg x mL(-1); p<0.001). During the same period, viral antigen persisted in the lungs of infected animals, although there was less inflammation at 6 weeks postinfection than at 1 week postinfection. In guinea-pigs, respiratory syncytial virus infection of the airways causes persistent airway hyperresponsiveness over a period of at least 5 weeks. During this time, viral antigen, but not inflammation, remains detectable in the lungs and might be responsible for ongoing airway hyperresponsiveness.
Riedel
F
F
Dept of Pediatrics, Ruhr-University Bochum, Germany.
Oberdieck
B
B
Streckert
H J
HJ
Philippou
S
S
Krusat
T
T
Marek
W
W
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001990:Bronchiolitis, Viral / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D013997:Time Factors
D000914:Antibodies, Viral; D000956:Antigens, Viral; D006632:Histamine