Topical anti-inflammatory activity of the glucocorticoid budesonide on airway mucosa. Evidence for a “hit and run” type of activity

Conclusions

• 1. The increase of macromolecular leakage from the airway mucosa into the airway lumen can be significantly counteracted by locally applied BUD 4 μg/kg.

• 2. The same dose of 4 μg/kg, when administered via intravenous route or to distal trachea and bronchi, is without effect on BRAD-induced leakage.

• 3. (1)–(2) imply that tracheally applied BUD exerts its anti-permability effect, at such a low dose, strictly at application site and does not act by the part available to the systemic or pulmonary-bronchial circulation. Probably, it influences directly tracheal epithelial lining and affects endothelium of tracheal postcapillary venules.

• 4. The anti-permeability action is not reproduced by 10 min superfusion with progesterone 3×10⁻⁶ M, supporting a selective GCS mechanism by topical BUD.

• 5. Our results suggest that inhalation of selected GCS will lead to a rapidly triggered but protracted anti-inflammatory action on airway mucosa. After triggering, the GCS can be absorbed and inactivated through biotransformation (“hit and run” type of activity).

• 6. The presented rat tracheal model permits the continuous and precise (area, time) topical application of drugs to airway mucosa. Permeability studies can then be performed on the same airway segment.