Effect of topical immunomodulators on acute allergic inflammation and bronchial hyperresponsiveness in sensitised rats

Tung Jung Huang, Paul Eynott, Michael Salmon, Paul L. Nicklin, K. Fan Chung

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

We examined the effects of different immunomodulators administered topically on asthmatic responses in a rat model of asthma. Sensitised Brown-Norway rats were administered rapamycin, SAR943 (32-deoxorapamycin), IMM125 (a hydroxyethyl derivative of D-serine8-cyclosporine), and budesonide by intratracheal instillation 1 h prior to allergen challenge. Allergen exposure induced bronchial hyperresponsiveness, accumulation of inflammatory cells in bronchoalveolar lavage fluid, and also an increase in eosinophils and CD2+, CD4+ and CD8+ T cells in the airways. Interleukin-2, interleukin-4, interleukin-5, interleukin-10, and interferon-γ mRNA expression was upregulated by allergen exposure. Budesonide abolished airway inflammation, suppressed the mRNA expression for interleukin-2, interleukin-4, and interleukin-5 (P<0.03), and bronchial hyperresponsiveness (P<0.05). IMM125 suppressed airway infiltration of eosinophils, and CD8+ T cells (P<0.02), and prevented the upregulated mRNA expression for interleukin-4, interleukin-5, and interferon-γ (P<0.02). Rapamycin suppressed CD8+ T cell infiltration in airway submucosa (P<0.03), and mRNA expression for interleukin-2 (p<0.002), while SAR943 suppressed interleukin-2, interleukin-4, and interferon-γ mRNA (P<0.05). IMM125, rapamycin and SAR943 did not alter airway submucosal CD2+ and CD4+ T cell infiltration, and bronchial hyperresponsiveness. CD8+ T cells, in contrast to CD4+ T cells, are more susceptible to the inhibition by IMM125 and rapamycin, which also caused greater suppression of Th1 compared to Th2 cytokine mRNA expression. In this acute model of allergic inflammation, differential modulation of Th1 and Th2 cytokines may determine the effects of various immunomodulators on airway inflammation and bronchial hyperresponsiveness.

Original languageEnglish
Pages (from-to)187-194
Number of pages8
JournalEuropean Journal of Pharmacology
Volume437
Issue number3
DOIs
StatePublished - 22 02 2002
Externally publishedYes

Keywords

  • Airway inflammation
  • Bronchial hyperresponsiveness
  • Budesonide
  • IMM125
  • Rapamycin
  • SAR943
  • Th1 cytokine
  • Th2 cytokine

Fingerprint

Dive into the research topics of 'Effect of topical immunomodulators on acute allergic inflammation and bronchial hyperresponsiveness in sensitised rats'. Together they form a unique fingerprint.

Cite this