IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

Proc Natl Acad Sci U S A. 2000 May 23;97(11):6007-12. doi: 10.1073/pnas.100118997.

Abstract

Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10-/-) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.

Publication types

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

MeSH terms

  • Aerosols
  • Animals
  • Blood Proteins / analysis
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cytokines / analysis
  • Electric Stimulation
  • Eosinophil Granule Proteins
  • Eosinophil Peroxidase
  • Eosinophilia / etiology
  • Eosinophilia / physiopathology
  • Female
  • Genetic Complementation Test
  • Genetic Therapy
  • Immunization
  • Inflammation / physiopathology
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Leukotrienes / analysis
  • Lung / chemistry
  • Lung / pathology
  • Male
  • Methacholine Chloride / administration & dosage
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth / physiopathology
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peroxidases / analysis
  • Respiratory Hypersensitivity / physiopathology*
  • Ribonucleases*
  • Specific Pathogen-Free Organisms
  • Trachea / physiopathology

Substances

  • Aerosols
  • Blood Proteins
  • Cytokines
  • Eosinophil Granule Proteins
  • Leukotrienes
  • Methacholine Chloride
  • Interleukin-10
  • Ovalbumin
  • Eosinophil Peroxidase
  • Peroxidases
  • Ribonucleases