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Low-dose dithranol treatment and tape stripping induce tolerance to dithranol in a mouse ear oedema model
1Department of Dermatology, Faculty of General Medicine, University of Szeged, Szeged, Hungary. kl@derma.szote.u-szeged.hu
Background:
It is well known from clinical practice that repeated treatment with dithranol leads to the development of tolerance.
Objectives:
To investigate the characteristics and mechanism of such dithranol tolerance.
Methods:
The mouse ear was pretreated with a low dose of dithranol or croton oil or, in previously sensitized animals, with dinitrofluorobenzene (DNFB). Twenty-four hours later irritant dermatitis was elicited by painting the mouse ear with a high dose of dithranol, croton oil or DNFB, and the dermatitis was characterized by measurement of ear thickness.
Results:
Low-dose dithranol significantly suppressed dithranol-induced oedema, whereas it had no effect on croton oil- or DNFB-induced dermatitis, suggesting that dithranol-induced tolerance is specific. Tolerance to dithranol could not be induced by pretreatment of the mouse ear with a low dose of croton oil or DNFB. Mild tape stripping of the mouse ear also inhibited the inflammatory effect of dithranol applied 24 h later. Superoxide dismutase treatment abolished the tolerance-inducing effect of low-dose dithranol or stripping.
Conclusions:
These results suggest that superoxide anion radicals are involved not only in the inflammatory effect of dithranol, but also in the induction of tolerance.