IL-12p40 and IL-18 modulate inflammatory and immune responses to respiratory syncytial virus infection

Academic Article


  • 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 -1-) 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-γ were not altered. Interestingly, IL-18, another mediator of IFN-γ 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-γ 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

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    Digital Object Identifier (doi)

    Author List

  • Wang SZ; Bao YX; Rosenberger CL; Tesfaigzi Y; Stark JM; Harrod KS
  • Start Page

  • 4040
  • End Page

  • 4049
  • Volume

  • 173
  • Issue

  • 6