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(Chest. 2003;124:671-681.)
© 2003 American College of Chest Physicians

Development of Respiratory Syncytial Virus "Bronchiolitis" in Guinea Pigs Does Not Reflect an Allergic Predisposition in the Host*

Andrew M. Bramley, PhD; M. Aatif Khan, MD; Heather E. Manson, MD, MHSc and Richard G. Hegele, MD, PhD, FCCP

* From UBC McDonald Research Laboratories and iCAPTURE Centre (Drs. Bramley, Khan, and Hegele), Department of Pathology and Laboratory Medicine, St. Paul’s Hospital, and The University of British Columbia, Department of Health Care and Epidemiology (Dr. Manson), Vancouver, BC, Canada.

Correspondence to: Richard G. Hegele, MD, PhD, FCCP, UBC McDonald Research Laboratories and iCAPTURE Centre, St. Paul’s Hospital, 1081 Burrard St, Vancouver, BC, Canada, V6Z 1Y6; e-mail: rhegele{at}mrl.ubc.ca

Background: Respiratory syncytial virus (RSV) infection causes bronchiolitis in a minority of children. Using a guinea pig model to determine if an allergic predisposition in the host increases permissiveness to RSV infection or severity of experimental "bronchiolitis," we compared the effects of RSV inoculation between strain 2 (allergy-resistant) and strain 13 (allergy-susceptible) inbred animals.

Methods: One month-old, juvenile guinea pigs were classified into four groups (eight guinea pigs per group): (group 1) strain 2, uninfected; (group 2) strain 13, uninfected; (group 3) strain 2, RSV infected; and (group 4) strain 13, RSV infected. Seven days after inoculation, the animals were studied by the following: viral plaque assays for quantification of intrapulmonary RSV; immunohistochemical localization of RSV antigens in lung tissue sections; physiologic assessment of airway obstruction and nonspecific bronchial hyperresponsiveness; quantitative histology of airway T lymphocytes, neutrophils, and eosinophils; and semiquantitative reverse transcriptase-polymerase chain reaction for levels of messenger RNA expression of a panel of proinflammatory cytokines and chemokines.

Results: Significantly higher titers of replicating RSV were isolated from the lungs of strain 13 vs strain 2 animals (p <= 0.001). The two guinea pig strains showed similar cell types with positive viral immunostaining; RSV-associated changes in airway obstruction and nonspecific bronchial hyperresponsiveness; airway T cells, neutrophils, and eosinophils; and messenger RNA expression of cytokines and chemokines.

Conclusions: Strain 13 guinea pigs show increased pulmonary RSV replication than strain 2 animals, but this increased permissiveness to the virus is not reflected by more severe virus-induced changes in airway obstruction, nonspecific bronchial hyperresponsiveness, airway inflammation, or gene expression of proinflammatory cytokines and chemokines.

Key Words: allergy • bronchial hyperresponsiveness • bronchiolitis • chemokines • cytokines • guinea pigs • inflammation • respiratory syncytial viruses • reverse transcriptase-polymerase chain reaction • strain 2 • strain 13




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F. Tayyari, T. C. Sutton, H. E. Manson, and R. G. Hegele
CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs
Eur. Respir. J., February 1, 2005; 25(2): 295 - 302.
[Abstract] [Full Text] [PDF]




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