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Respiratory syncytial virus (RSV) induces airway insensitivity to β‐agonists in BALB/c mice
Author(s) -
Davis Ian Christopher,
Traylor Zachary P.,
Yu Erin N. Z.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1062.1
Subject(s) - terbutaline , bronchiolitis , immunology , bronchoalveolar lavage , medicine , methacholine , neutralizing antibody , bronchoconstriction , ovalbumin , agonist , respiratory system , heterologous , antibody , pharmacology , receptor , virus , lung , asthma , chemistry , respiratory disease , immune system , biochemistry , gene
Beta‐adrenergic agonists (β‐agonists) are commonly used to treat RSV bronchiolitis, but are generally ineffective. We have previously shown that RSV strain A2 inhibits bronchoalveolar epithelial responses to β‐agonists in BALB/c mice. The aim of the current study was to determine whether RSV also induces airway insensitivity to β‐agonists. Total lung resistance was measured in anesthetized female BALB/c mice on a flexiVent ventilator. RSV A2 did not induce airway hyperresponsiveness to increasing doses of nebulized methacholine (MCH) at any timepoint. Prenebulization with the β‐agonist terbutaline (100 μM) significantly attenuated bronchoconstrictive responses to MCH in uninfected mice and in mice infected with RSV for 4–8 days. However, in mice infected with replication‐competent, but not UV‐inactivated, RSV for 2 days, significant terbutaline insensitivity was found. Terbutaline insensitivity could be reversed by I.P. treatment with neutralizing anti‐CXCR2 antibodies (which reduced BAL neutrophil counts, but not viral replication), or by post‐infection nebulization with neutralizing anti‐KC or anti‐CXCR2 antibodies, and could be replicated in normal, uninfected mice by nebulized recombinant KC. These data suggest that KC/CXCR2‐mediated heterologous desensitization of β‐adrenergic receptors may underlie the modest utility of these drugs as bronchodilators in RSV bronchiolitis.