Dendritic cells modulated by cytokine-expressing adenoviruses alleviate eosinophilia and airway hyperresponsiveness in an animal model of asthma

J Allergy Clin Immunol. 2004 Jul;114(1):88-96. doi: 10.1016/j.jaci.2004.03.010.

Abstract

Background: It has been found that TH1-related cytokines can decrease the accumulation of eosinophils in lung tissue and relieve airway constriction.

Objective: Dendritic cells (DCs) have been found to prime naive T-helper cells efficiently. In this study, DCs infected with TH1 cytokine-expressing adenovirus can be used to induce antigen-specific TH1 cells for treatment in an animal model of asthma.

Methods: Cytokine gene-modulated DCs pulsed with ovalbumin antigen (OVA) were injected intravenously into naive mice 1 week before sensitization with OVA antigen. The mice were then monitored for OVA-specific IgE, airway inflammatory cell infiltration, and airway hyperresponsiveness in the study.

Results: Significant levels of IL-12 or IL-18 were expressed by Ad-IL-12 or Ad-IL-18 infected, bone marrow-derived DCs. Ad-IL-12 and Ad-IL-18 co-infected DCs effectively, decreasing sera anti-OVA IgE antibody levels, lung eosinophilia, and airway hyperresponsiveness.

Conclusion: We concluded that DCs modulated by TH1-prone cytokine-expressing adenoviruses can alleviate TH2-type airway inflammation in a murine model and can provide possible therapeutic application for DCs in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Animals
  • Asthma / complications
  • Asthma / immunology*
  • Bronchial Hyperreactivity / complications
  • Bronchial Hyperreactivity / immunology*
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Eosinophilia / complications
  • Eosinophilia / immunology*
  • Interleukin-12 / immunology
  • Interleukin-18 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Cytokines
  • Interleukin-18
  • Interleukin-12