Chronic postbronchiolitis airway instability induced with anti-IFN-gamma antibody in F344 rats.
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-gamma (IFN-gamma); we hypothesized that the normally resistant F344 rat strain would develop the asthmalike phenotype if the IFN-gamma response were suppressed during viral illness. Weanling F344 rats were pretreated with anti-IFN-gamma or control antibody, and inoculated with Sendai virus or vehicle. Anti-IFN-gamma treatment reduced lung IFN-gamma 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-gamma 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-gamma 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.
Sorkness
Ronald L
RL
Division of Allergy and Immunology, Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA. RLSORKNE@facstaff.wisc.edu
Castleman
William L
WL
Mikus
Lance D
LD
Mosser
Anne G
AG
Lemanske
Robert F
RF
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001249:Asthma / Q000503:physiopathology*; D001988:Bronchiolitis / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002908:Chronic Disease; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000906:Antibodies; D007371:Interferon-gamma