Tacrolimus Ointment for Atopic Dermatitis

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Abstract
Ruzicka et al. (Sept. 18, 1997, issue)1 reported that tacrolimus (FK 506) ointment is beneficial in the treatment of atopic dermatitis. It is remarkable that an immunosuppressant agent produced a significant improvement in the symptoms of an inflammatory disease after three days of treatment. I suggest that in this disorder, which is characterized by the activation of skin mast cells and infiltrating basophils,2 tacrolimus acts as an antiinflammatory agent by modulating the release of inflammatory mediators. Mast cells and basophils act as both immunoregulators and proinflammatory cells through the release of vasoactive mediators and cytokines (e.g., interleukin-4). Basophils from patients with atopic dermatitis have an increase in the release of histamine after exposure to immunologic and nonimmunologic stimuli.3 Pharmacologic concentrations of tacrolimus exert antiinflammatory effects by inhibiting the immunologically stimulated release of histamine and other proinflammatory agents from basophils4 and skin mast cells.5 Recently, my colleagues and I found that tacrolimus also inhibits the immunologically mediated generation of interleukin-4 from basophils.6 These results, together with the finding that cyclosporine, which also acts on the calcium–calcineurin pathway that regulates the secretion of basophils and mast cells,4,5 suggest that immunophilin-binding drugs are potent antiinflammatory agents.5 Therefore, although tacrolimus has remarkable properties of immunosuppression, its rapid antiinflammatory effect in patients with atopic dermatitis1 is most likely mediated by its effects on the release of proinflammatory and vasoactive mediators from skin mast cells and infiltrating basophils.2 Therefore, patients with other inflammatory skin disorders involving these cells might also benefit from treatment with these compounds.