title: 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.
abstract: A distinct clinical presentation of respiratory syncytial virus (RSV) infection of humans is bronchiolitis, which has clinical features similar to those of asthma. Substance P (SP), a tachykinin neuropeptide, has been associated 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 and the effect of anti-SP F(ab)(2) antibodies on the pulmonary inflammatory response. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatment 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 infection. In mice challenged after formalin-inactivated RSV vaccination, SP appears to markedly enhance pulmonary eosinophilia as well as increase polymorphonuclear cell trafficking to the lung. Based on studies with a strain of RSV 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 that 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.
authors.affiliation: Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. rgt3@cdc.gov
authors.forename: R A
authors.initials: RA
authors.lastname: Tripp
authors.forename: D
authors.initials: D
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.forename: L J
authors.initials: LJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001988:Bronchiolitis / Q000276:immunology* / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D017252:CD3 Complex / Q000276:immunology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015707:HN Protein; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D013373:Substance P / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D017252:CD3 Complex; D016207:Cytokines; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D013373:Substance P