Respiratory syncytial virus infection prolongs methacholine-induced airwayhyperresponsiveness in ovalbumin-sensitized mice

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined models of allergen sensitization a nd RSV infection to begin exploring the immunologic interactions between al lergic and virus-induced airway inflammation and its impact on airway hyper sensitivity. Airway resistance was measured after methacholine challenge in tracheally intubated mice by whole body plethysmography. Lung inflammation was assessed by bronchoalveolar lavage (BAL) and histopathology. RSV infec tion alone did not cause significant airway hyperresponsiveness (AHR) to me thacholine. Ovalbumin (OVA)induced AHR lasted only a few days past the disc ontinuance of OVA aerosol in mice that were ovalbumin sensitized and mock i nfected. In contrast, OVA-sensitized mice infected with RSV during the OVA aerosol treatments (OVA/RSV) had AHR for more than 2 weeks after infection. However, 2 weeks after either RSV or mock infection, OVA/RSV mice had sign ificantly more lymphocytes found during BAL than OVA mice, whereas the OVA and OVA/RSV groups had the same number of eosinophils. Histopathologic anal ysis confirmed an increased inflammation in the lungs of OVA/RSV mice compa red with OVA mice. In addition, OVA/RSV mice had a more widespread distribu tion of mucus in their airways with increased amounts of intraluminal mucus pools compared with the other groups. Thus, prolonged AHR in RSV-infected mice during ovalbumin-sensitization correlates with increased numbers of ly mphocytes in BAL fluid, increased lung inflammation, and mucus deposition i n the airways, but not with airway eosinophilia. A further understanding of the immunologic consequences of combined allergic and virus-induced airway inflammation will impact the management of diseases associated with airway hyperreactivity. (C) 1999 Wiley-Liss, Inc.