EFFECTS OF TOPICAL BUDESONIDE ON EPITHELIAL RESTITUTION IN-VIVO IN GUINEA-PIG TRACHEA

Background - Continuous epithelial shedding and restitution processes may characterise the airways in diseases such as asthma. Epithelial re stitution involves several humoral and cellular mechanisms that may po tentially be affected by inhaled anti-asthma drugs. The present study examines the effect of a topical steroid on epithelial restitution in vivo in the guinea pig. Methods - The airway epithelium was mechanical ly removed from well defined areas of guinea pig trachea without surge ry and without damage to the basement membrane or bleeding. An anti-in flammatory dose of budesonide (1 mg) was administered repeatedly to th e tracheal surface by local superfusion 24 hours before, at (0 hours), and 24 hours after the denudation. Migration of epithelial cells, for mation of a plasma exudation-derived gel, and appearance of luminal le ucocytes were recorded by scanning electron microscopy. Cell prolifera tion was visualised by bromodeoxyuridine immunohisto-chemistry and tis sue neutrophils and eosinophils by enzyme histochemistry. Results - Im mediately after creation of the denuded zone ciliated and secretory ce lls on its border dedifferentiated, flattened out, and migrated speedi ly (mean (SE) 2 3 (0 3) mu m/min) over the basement membrane. After 48 hours the entire denuded zone (800 mu m wide) was covered by a tightl y sealed epithelium; at this time increased proliferation was observed in new and old epithelium and subepithelial cells. Budesonide had no detectable effect on epithelial sealing, after denudation and continuo usly during the migration phase plasma was extravasated creating a fib rinous gel rich in leucocytes, particularly neutrophils, over the denu ded area. Budesonide had no effect on either the gel or the leucocyte density. Conclusions - These observations suggest that topical glucoco rticoids may not interfere with a fast and efficient restitution of th e epithelium in the airways.