YM-341619 suppresses the differentiation of spleen T cells into Th2 cells in vitro, eosinophilia, and airway hyperresponsiveness in rat allergic models

Eur J Pharmacol. 2008 Aug 20;590(1-3):409-16. doi: 10.1016/j.ejphar.2008.06.035. Epub 2008 Jun 14.


T helper (Th) 2 cells play a central role in the pathogenesis of allergic diseases such as allergic asthma, atopic dermatitis, and allergic rhinitis. We have found that YM-341619 hydrochloride, which suppressed IL-4-induced STAT6-dependent reporter gene expression, inhibited the differentiation of mouse spleen T cells into Th2 cells in vitro. YM-341619 suppressed the production of IL-4 and the expression of GATA-3 mRNA, a Th2 transcription factor, in T cells cultured with anti-CD3 antibody and anti-CD28 antibody in the presence of IL-4. In contrast, the production of IFN-gamma and the expression of T-bet mRNA, a Th1 transcription factor, in T cells cultured with anti-CD3 antibody in the presence of IL-12, were not effected by YM-341619. Orally administered YM-341619 (0.003-0.03 mg/kg) reduced the plasma IgE level of DNP-Ascaris-sensitized rats, but not the IgG(2a) level. YM-341619 suppressed IL-4 and IL-13 production in the splenocytes of these DNP-Ascaris-sensitized rats without augmenting IFN-gamma production. YM-341619 also dose-dependently suppressed eosinophil accumulation in the lung (0.003-3 mg/kg, p.o.) and airway hyperresponsiveness (0.3-3 mg/kg, p.o.) induced by repeated exposure to ovalbumin in ovalbumin-sensitized rats. These results suggest that YM-341619 has the ability to suppress allergen-induced Th2 responses by selectively inhibiting the differentiation of CD4(+) T cells into the Th2 subset.

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Asthma / immunology
  • Bronchial Hyperreactivity / drug therapy*
  • Cell Differentiation / drug effects
  • Dose-Response Relationship, Drug
  • Eosinophilia / drug therapy*
  • Female
  • GATA3 Transcription Factor / genetics
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / biosynthesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology*
  • Morpholines / therapeutic use
  • Promoter Regions, Genetic
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Rats
  • Rats, Inbred BN
  • Rats, Wistar
  • STAT6 Transcription Factor / genetics
  • Spleen / cytology*
  • T-Lymphocytes / cytology*
  • Th2 Cells / cytology*


  • 2-((4-morpholin-4-ylphenyl)amino)-4-((2,3,6-trifluorobenzyl)amino)pyrimidine-5-carboxamide
  • GATA3 Transcription Factor
  • Morpholines
  • Pyrimidines
  • STAT6 Transcription Factor
  • Interleukin-4
  • Interferon-gamma