Evidence suggests that both host and viral factors influence disease severi
ty after infection with respiratory syncytial virus (RSV), To characterize
the effects of pertussis toxin (PT) sensitization on subsequent RSV infecti
on, BALB/c mice were treated with PT parenterally before RSV challenge. Pri
ming with purified and detoxified PT before RSV challenge increased postcha
llenge weight loss and mortality. PT priming changed the kinetics, location
, and composition of the cellular infiltrate in the lung but altered neithe
r antibody responses nor virus titers, Passive transfer of PT-sensitized sp
lenocytes produced similar responses. Priming with purified, but not geneti
cally detoxified, PT propagated a modest type 2 cytokine response to RSV an
tigens. However, anti-interleukin-4 treatment before RSV challenge failed t
o abrogate the effects of PT priming, These data confirm that the preexisti
ng immune environment can change virus-specific immunity and provide both a
model for study of RSV disease and evidence that noninfectious immunomodul
ators may impact pathogen-specific immunity.