Abstract
Analogous to childhood-onset asthma in humans, rats may develop a chronic asthmalike phenotype, depending on their genetic background and the age at which they experience a viral airway injury. Brown Norway rats develop a postbronchiolitis asthmalike phenotype that may be prevented with supplements of interferon-γ (IFN-γ); we hypothesized that the normally resistant F344 rat strain would develop the asthmalike phenotype if the IFN-γ response were suppressed during viral illness. Weanling F344 rats were pretreated with anti-IFN-γ or control antibody, and inoculated with Sendai virus or vehicle. Anti-IFN-γ treatment reduced lung IFN-γ and increased IL-4 mRNA during the infection. Physiologic studies performed 8 wk later revealed premature airway closure (p = 0.03) and elevated specific pulmonary resistance (p < 0.01) in the postbronchiolitis anti-IFN-γ group compared with noninfected controls and untreated postbronchiolitis rats. However, unlike the postbronchiolitis asthmalike phenotype in Brown Norway rats, bronchiolar inflammation and fibrosis were absent in the F344 rats. Lung elastic recoil and alveolar surface density also were unchanged compared with noninfected control rats. We conclude that there is an interactive effect of a weak IFN-γ response and viral bronchiolitis at an early age that may result in persistent postbronchiolitis airway dysfunction. The presence of premature airway closure that is independent of airway wall inflammation or changes in lung elastic recoil suggests peripheral airway instability as a mechanism for the airway obstruction.
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Abbreviations
- BN:
-
Brown Norway inbred rat strain
- F344:
-
Fischer 344 inbred rat strain
- IFN-γ:
-
interferon-γ
- BAL:
-
bronchoalveolar lavage
- TLC:
-
total lung capacity
- RV:
-
residual lung volume
- sRL:
-
specific pulmonary resistance
- PC0.2:
-
concentration of aerosolized methacholine producing an increase in pulmonary resistance of 0.2 hPa·mL−1·s
- LSD:
-
least significant difference
- IFR-1:
-
IFN regulatory factor 1
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Supported by NIH grants AI-34891 and HL-56396.
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Sorkness, R., Castleman, W., Mikus, L. et al. Chronic Postbronchiolitis Airway Instability Induced with Anti-IFN-γ Antibody in F344 Rats. Pediatr Res 52, 382–386 (2002). https://doi.org/10.1203/00006450-200209000-00013
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DOI: https://doi.org/10.1203/00006450-200209000-00013
