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

J Immunol. 2004 Sep 15;173(6):4040-9. doi: 10.4049/jimmunol.173.6.4040.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / antagonists & inhibitors
  • Adjuvants, Immunologic / deficiency
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / physiology*
  • Alcian Blue / analysis
  • Animals
  • Antibodies, Blocking / administration & dosage
  • Bronchiolitis, Viral / genetics
  • Bronchiolitis, Viral / immunology
  • Bronchiolitis, Viral / pathology
  • Bronchiolitis, Viral / virology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / virology
  • CD3 Complex / biosynthesis
  • Cytokines / biosynthesis
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / immunology
  • Inflammation Mediators / physiology*
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-12 / physiology*
  • Interleukin-12 Subunit p40
  • Interleukin-18 / antagonists & inhibitors
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / immunology
  • Interleukin-18 / physiology*
  • Leukocyte Count
  • Lung / immunology
  • Lung / metabolism
  • Lung / virology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mucus / chemistry
  • Mucus / immunology
  • Mucus / metabolism
  • Neutralization Tests
  • Periodic Acid-Schiff Reaction
  • Protein Subunits / deficiency
  • Protein Subunits / genetics
  • Protein Subunits / immunology
  • Protein Subunits / physiology*
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Up-Regulation / genetics
  • Up-Regulation / immunology
  • Viral Load

Substances

  • Adjuvants, Immunologic
  • Antibodies, Blocking
  • CD3 Complex
  • Cytokines
  • Inflammation Mediators
  • Interleukin-12 Subunit p40
  • Interleukin-18
  • Protein Subunits
  • Interleukin-12
  • Interferon-gamma
  • Alcian Blue