Th17 immunity in children with allergic asthma and rhinitis: a pharmacological approach

PLoS One. 2013;8(4):e58892. doi: 10.1371/journal.pone.0058892. Epub 2013 Apr 3.

Abstract

Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss), nasal wash (NW) and plasma (P) from Healthy Controls (HC) and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t) and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested "in vitro" on IL-17A, RORγ(t) and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of 12 weeks of treatment with Budesonide and Formoterol was tested "in vivo" in T-lymphocytes from mild-moderate asthma/persistent rhinitis patients. IL-17A was increased in Ss, NW and P from children with mild-moderate asthma compared with intermittent and HC. In cultured T-lymphocytes IL-17A and RORγ(t) expression were higher in mild-moderate asthma/persistent rhinitis than in mild-moderate asthma/intermittent rhinitis, while FOXP3 was reduced. Budesonide with Formoterol reduced IL-17A and RORγ(t), while increased FOXP3 in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis, and reduced the IL-8 release mediated by IL-17A present in NW and Ss from mild-moderate asthma/persistent rhinitis in nasal and bronchial epithelial cells. Finally, Budesonide with Formoterol reduced IL-17A levels in P and Ss, CD4(+)IL-17A(+)T-cells, in naïve children with mild-moderate asthma/persistent rhinitis after 12 weeks of treatment. Th17 mediated immunity may be involved in the airway disease of children with allergic asthma and allergic rhinitis. Budesonide with Formoterol might be a useful tool for its therapeutic control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / pharmacology*
  • Asthma / drug therapy
  • Asthma / immunology*
  • Asthma / metabolism
  • Budesonide / administration & dosage
  • Budesonide / pharmacology*
  • Case-Control Studies
  • Cells, Cultured
  • Child
  • Ethanolamines / administration & dosage
  • Ethanolamines / pharmacology*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Formoterol Fumarate
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Nasal Lavage Fluid
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Rhinitis, Allergic, Perennial / drug therapy
  • Rhinitis, Allergic, Perennial / immunology*
  • Rhinitis, Allergic, Perennial / metabolism
  • Sputum / metabolism
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Ethanolamines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL17A protein, human
  • Interleukin-17
  • Interleukin-8
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Budesonide
  • Formoterol Fumarate

Grants and funding

The research funds received by M. Profita were from the Italian National Research Council.