Prolonged topical application of tacrolimus inhibits immediate hypersensitivity reactions by reducing degranulation of mast cells.

We studied the effects of prolonged topical application of tacrolimus on immediate hypersensitivity reactions. Tacrolimus, betamethasone or petrolatum was applied to the footpad of mice for up to 28 days after immunization, and the foot-swelling response to allergen was estimated. The reactions in tacrolimus-treated mice decreased significantly from day 14, while those in betamethasone-treated mice decreased significantly from day 7. Although the number of mast cells in the foot skin of each group did not differ significantly, the percentage of degranulated mast cells decreased in the tacrolimus-treated group on days 7 and 14. The TUNEL method indicated that there were no apoptotic mast cells in the foot skin of tacrolimus-treated mice. Continuous application of topical tacrolimus ointment may suppress immediate hypersensitivity reactions by reducing the degranulation of mast cells, rather than by decreasing their number.