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-gamma (IFN-gamma). These findings are consistent with an
eosinophilia orchestrated by activated Th2-type cells. 3.
RPR 106541 (10-300 microg 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 microg kg[-1]) caused a significant (P<0.01) (98%) inhibition of eosinophil influx and a significant (P<0.01) (100%) inhibition of neutrophil influx.
RPR 106541 was approximately 7 times and 4 times more potent than
budesonide and
fluticasone propionate, respectively. 4. When tested at a single dose (300 microg kg[-1]),
RPR 106541 and
fluticasone each caused a significant (P<0.01) (100%) inhibition of CD4+ T cell accumulation in lung tissue.
Budesonide (300 microg kg[-1]) had no significant effect.
RPR 106541 and
fluticasone (300 microg kg[-1]), but not
budesonide (300 microg kg[-1]), significantly (P<0.05) inhibited the expression within lung tissue of
mRNA for
IL-4.
RPR 106541 (300 microg kg[-1]) also significantly (P<0.05) inhibited expression of
mRNA for
IL-5. 5. The high topical potency of
RPR 106541 in this model, which mimics important aspects of airway
inflammation in human allergic asthmatics, suggests that this
glucocorticoid may be useful in the treatment of
bronchial asthma.