In several clinical studies topical immunomodulators have been shown to be effective in the treatment of atopic dermatitis (AD). As calcineurin inhibitors, they directly act on T cells by inhibiting the transcription of cytokines. We examined the cellular infiltrate of skin lesions of 10 AD patients and characterized the cytokine pattern expressed by the infiltrating cells before and after therapy with topical tacrolimus 1% ointment b.i.d..

Systemic effects were assessed by differential white blood cell counts, immunophenotyping, and functional T cell tests, such as lymphocyte proliferation and cytokine production. Skin biopsies were examined for histological alterations (HE staining), composition of inflammatory infiltrate (immunofluorescence) and cytokine expression (immunofluorescence, ELISA).

All patients showed a significant clinical improvement of their skin lesions. In the peripheral blood, a decrease of leucocytes, including eosinophils and neutrophils, was noticed. Immunophenotyping suggested no alterations in the distribution of lymphocyte subpopulations. Histological examination revealed a marked regression of spongiosis, acanthosis and density of the inflammatory infiltrate in the dermis. The numbers of T cells and eosinophils as well as their expression of T helper 2 cytokines were reduced after therapy. In contrast, the number of epidermal CD1a positive cells increased as a consequence of topical tacrolimus treatment.

Our results suggest that topical tacrolimus mediates dramatic anti-inflammatory effects within the skin of AD patients without causing systemic immunosuppression.