Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma

Gene Ther. 2006 Oct;13(19):1414-21. doi: 10.1038/sj.gt.3302798. Epub 2006 May 25.

Abstract

Interleukin-1 (IL-1) is a proinflammatory cytokine and IL-1 receptor antagonist (IL-1ra) is a natural inhibitor that binds to IL-1 receptor type I without inducing signal transduction. It is suggested that IL-1 is required for allergen-specific T helper type 2 cell activation and the development of airway hyper-responsiveness (AHR), but the immunologic effect of exogenous IL-1ra in allergic asthma remains unclear. To examine the effect of IL-1ra on airway inflammation and immunoeffector cells in allergic asthma, recombinant adenovirus expressing human IL-1ra (Ad-hIL-1ra) was delivered intranasally into ovalbumin (OVA)-immunized mice. Single intranasal administration of Ad-hIL-1ra before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and reduced pulmonary infiltration of eosinophils and neutrophils. Suppression of IL-5 and eotaxin with concomitant enhancement of interferon gamma in bronchoalveolar lavage fluid was also noted in OVA-immunized mice by administration of Ad-hIL-1ra. In addition, histological studies showed that Ad-hIL-1ra was able to decrease OVA-induced peribronchial inflammation. Taken together, our results indicated that administration of Ad-hIL-1ra may have therapeutic potential for the immunomodulatory treatment of allergic asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Administration, Inhalation
  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / therapy*
  • Bronchi / immunology*
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemokine CCL11
  • Chemokines, CC / analysis
  • Female
  • Genetic Engineering
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Hypersensitivity / immunology
  • Hypersensitivity / therapy
  • Interferon-gamma / analysis
  • Interleukin 1 Receptor Antagonist Protein / analysis
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin-5 / analysis
  • Lung / immunology
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Ovalbumin
  • Th2 Cells / immunology
  • Transduction, Genetic / methods

Substances

  • CCL11 protein, human
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Chemokines, CC
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-5
  • Interferon-gamma
  • Ovalbumin