Low dose oral administration of cytokines for treatment of allergic asthma

Pulm Pharmacol Ther. 2009 Dec;22(6):497-510. doi: 10.1016/j.pupt.2009.05.002. Epub 2009 May 21.

Abstract

Many inflammatory diseases are characterized by an imbalance among lymphocyte populations, in particular Th1, Th2 and the recently described Th17 cells. The Th1/Th2 imbalance is linked to many factors, but certainly the role of cytokines is essential. In Th2 diseases IL-4 expression is predominant, while Th1 pathologies are characterized by high expression of IFN-gamma and IL-12. Though today the therapeutical proposal for many inflammatory diseases aims to re-establish normal levels of Th1/Th2 cytokines, the pharmacological use of cytokines, which are very active molecules, is limited by the possible collateral effects. Therefore, our study aims to determine, in a murine model of allergic asthma, the possible therapeutic activity of low dose cytokines solutions, mechanically activated. We found that oral administration of low doses IL-12 plus IFN-gamma is able to solve the bronchial hyperresponsiveness condition of mice, establishing normal cytokine levels. The anti-asthma activity was confirmed by histological analysis of lungs and broncho-alveolar lavage fluid cell count. Serum ovalbumin-specific IgE was also significantly inhibited by treatment with low dose activated cytokines solution. These findings may suggest a novel approach to diseases which involve a Th1/Th2 imbalance.

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Asthma / pathology
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • CD11c Antigen / immunology
  • Cytokines / administration & dosage
  • Cytokines / therapeutic use*
  • Dendritic Cells / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / therapeutic use*
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / therapeutic use*
  • Lung / immunology
  • Lung / pathology
  • Male
  • Mice
  • Recombinant Proteins / therapeutic use
  • Respiratory Hypersensitivity / drug therapy*
  • Respiratory Hypersensitivity / pathology
  • Solutions
  • Spleen / cytology
  • Spleen / drug effects
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • CD11c Antigen
  • Cytokines
  • Recombinant Proteins
  • Solutions
  • Interleukin-12
  • Interferon-gamma