Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection: Eosinophils mediate airway hyperresponsiveness, M-2 muscarinic receptor dysfunction, and antiviral effects

Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia. This may reflect altered inflammatory response to viru ses in atopic individuals. Inhibitory M-2 muscarinic receptors (M(2)Rs) on the airway parasympathetic nerves limit acetylcholine release. Both viral i nfection and inhalational antigen challenge cause M2R dysfunction, leading to airway hyperresponsiveness. Ill antigen-challenged, but not virus-infect ed guinea pigs, M2R dysfunction is due to blockade of the receptors by the endogenous antagonist eosinophil major basic protein (MBP). We hypothesized that sensitization to a nonviral antigen bt iol-e viral infection alters t he inflammatory response to viral infection, so that M2R dysfunction and hy perreactivity are eosinophil mediated. Guinea pigs were sensitized to ovalb umin intraperitoneally, and 3 wk later were infected with parainfluenza. In sensitized, but not in nonsensitized animals, virus-induced hyperresponsiv eness and M2R dysfunction were blocked by depletion of eosinophils with ant ibody to interleukin (IL)-5 or treatment with antibody to MBP, An additiona l and unexpected finding was that sensitization to ovalbumin caused a marke d (80%) reduction in the viral content of the lungs. This was reversed by t he antibody to IL-5, implicating a role,, eosinophils in viral immunity.