title: IL-12p40 and IL-18 modulate inflammatory and immune responses to respiratory syncytial virus infection.
abstract: Respiratory syncytial virus-induced bronchiolitis has been linked to the development of allergy and atopic asthma. IL-12 and possibly IL-18 are central mediators orchestrating Th1 and/or Th2 immune responses to infection. To determine a possible role for IL-12 in regulating the immune response to acute respiratory syncytial virus infection, IL-12p40 gene-targeted (IL-12p40-/-) and wild-type mice were intratracheally infected with respiratory syncytial virus, and lung inflammatory and immune responses were assessed. Lung inflammation and mucus production were increased in the airways of IL-12p40-/- mice as compared with those of wild-type mice, concurrent with increased levels of the Th2 effector cytokines IL-5 and IL-13. Respiratory syncytial virus clearance and levels of Th1 effector cytokine IFN-gamma were not altered. Interestingly, IL-18, another mediator of IFN-gamma production, was significantly increased in the lungs of IL-12p40-/- mice early during the course of infection. Abrogation of IL-18-mediated signaling in IL-12p40-/- mice further enhanced Th2 immune response and mucus production in the airways during respiratory syncytial virus infection but failed to modulate IFN-gamma production or viral clearance. These findings implicate a role for IL-12 and IL-18 in modulating respiratory syncytial virus-induced airway inflammation distinct from that of viral clearance.
authors.affiliation: Asthma and Pulmonary Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors.forename: Shan-Ze
authors.initials: SZ
authors.lastname: Wang
authors.forename: Yi-Xiao
authors.initials: YX
authors.lastname: Bao
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Rosenberger
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: James M
authors.initials: JM
authors.lastname: Stark
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Harrod
mesh_terms: D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000423:Alcian Blue / Q000032:analysis; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001990:Bronchiolitis, Viral / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000821:virology; D017252:CD3 Complex / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D009500:Neutralization Tests; D010503:Periodic Acid-Schiff Reaction; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D017252:CD3 Complex; D016207:Cytokines; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma; D000423:Alcian Blue