A role for airway remodeling during respiratory syncytial virus infection.
BACKGROUND
Severe respiratory syncytial virus infection (RSV) during infancy has been shown to be a major risk factor for the development of subsequent wheeze. However, the reasons for this link remain unclear. The objective of this research was to determine the consequences of early exposure to RSV and allergen in the development of subsequent airway hyperreactivity (AHR) using a developmental time point in the mouse that parallels that of the human neonate.


METHODS
Weanling mice were sensitized and challenged with ovalbumin (Ova) and/or infected with RSV. Eight days after the last allergen challenge, various pathophysiological endpoints were examined.


RESULTS
AHR in response to methacholine was enhanced only in weanling mice exposed to Ova and subsequently infected with RSV. The increase in AHR appeared to be unrelated to pulmonary RSV titer. Total bronchoalveolar lavage cellularity in these mice increased approximately two-fold relative to Ova alone and was attributable to increases in eosinophil and lymphocyte numbers. Enhanced pulmonary pathologies including persistent mucus production and subepithelial fibrosis were observed. Interestingly, these data correlated with transient increases in TNF-alpha, IFN-gamma, IL-5, and IL-2.


CONCLUSIONS
The observed changes in pulmonary structure may provide an explanation for epidemiological data suggesting that early exposure to allergens and RSV have long-term physiological consequences. Furthermore, the data presented here highlight the importance of preventative strategies against RSV infection of atopic individuals during neonatal development.
Becnel
David
D
Department of Biological Sciences, 202 Life Sciences Bldg., Baton Rouge, LA 70803, USA. dbecne1@lsu.edu
You
Dahui
D
Erskin
Joshua
J
Dimina
Dawn M
DM
Cormier
Stephania A
SA
D000818:Animals; D001985:Bronchial Provocation Tests; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification*
D016210:Methacholine Chloride; D010047:Ovalbumin