RPR 106541, a novel, airways‐selective glucocorticoid: effects against antigen‐induced CD4+T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung

Abstract

1 The effects of a novel 17‐thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. 2 In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4⁺ T lymphocytes and increased expression of mRNA for interleukin‐4 (IL‐4) and IL‐5, but not interferon‐γ (IFN‐γ). These findings are consistent with an eosinophilia orchestrated by activated Th2‐type cells. 3 RPR 106541 (10–300 μg kg⁻¹), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose‐dependently inhibited cell influx into the airway lumen. RPR 106541 (100 μg kg⁻¹) caused a significant (PP−1), RPR 106541 and fluticasone each caused a significant (P+ T cell accumulation in lung tissue. Budesonide (300 μg kg⁻¹) had no significant effect. RPR 106541 and fluticasone (300 μg kg⁻¹), but not budesonide (300 μg kg⁻¹), significantly (P−1) also significantly (PBritish Journal of Pharmacology (1997) 122, 439–446; doi:10.1038/sj.bjp.0701398