Low-dose dithranol treatment and tape stripping induce tolerance to dithranol in a mouse ear oedema model

Br J Dermatol. 2002 May;146(5):764-9. doi: 10.1046/j.1365-2133.2002.04663.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anthralin / administration & dosage
  • Anthralin / toxicity*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / toxicity*
  • Croton Oil / toxicity
  • Dinitrofluorobenzene / toxicity
  • Drug Administration Schedule
  • Drug Eruptions / prevention & control*
  • Drug Tolerance
  • Ear Diseases / chemically induced*
  • Ear, External
  • Edema / chemically induced*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Superoxide Dismutase / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Croton Oil
  • Dinitrofluorobenzene
  • Superoxide Dismutase
  • Anthralin