Respiratory syncytial virus infection and G and/or SH protein expression contribute to substance P, which mediates inflammation and enhanced pulmonary disease in BALB/c mice

A distinct clinical presentation of respiratory syncytial virus (RSV) infec tion of humans is bronchiolitis, which has clinical features similar to tho se of asthma, Substance P (SP), a tachykinin neuropeptide, has been associa ted with neurogenic inflammation and asthma; therefore, we chose to examine SP-induced inflammation with RSV infection. In this study, we examined the production of pulmonary SP associated with RSV infection of BALB/c mice an d the effect of anti-SP F(ab)(2) antibodies on the pulmonary inflammatory r esponse. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatm ent of RSV-infected mice with anti-SP F(ab)(2) antibodies suggested that SP may alter the natural killer cell response to primary and secondary infect ion. In mice challenged after formalin-inactivated RSV vaccination, SP appe ars to markedly enhance pulmonary eosinophilia as well as increase polymorp honuclear cell trafficking to the lung. Eased on studies with a strain of R SV that lacks the G and SH genes, the SP response to RSV infection appears to be associated with G and/or SH protein expression. These data suggest th at SP may be an important contributor to the inflammatory: response to RSV infection and that anti-SP F(ab)(2) antibodies might be used to ameliorate RSV-associated disease.