Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment

BACKGROUND: In several clinical studies, topical calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis (AD). They target signaling pathways that control gene expression, particularly the expression of cytokines. OBJECTIVE: We examined the cellular infiltrate in skin lesions of 10 patients with AD and characterized the cytokine pattern expressed by the infiltrating cells before and after short-term topical therapy with tacrolimus 1% ointment. METHODS: Skin biopsies were examined for histologic alterations (hematoxylin and eosin staining), composition of the cellular inflammatory infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD and normal skin were analyzed. Systemic immunologic effects were assessed by analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro stimulated pan-T-cell cytokine production (ELISA). RESULTS: All patients showed a significant improvement of their skin lesions associated with a marked regression of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis. The last was a result of reduced infiltration of T cells, B cells, and eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the expression of the T H 2 cytokines IL-5, IL-10, and IL-13 in CD4 + T cells was reduced after therapy. Interestingly, tacrolimus therapy was also associated with a reduction of CD8 + T cells expressing the T H 1 cytokine IFN-gamma. Furthermore, the numbers of epidermal CD1a + dendritic cells increased after treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and neutrophils) but no changes in the distribution of lymphocyte subpopulations were noticed. CONCLUSION: Topical tacrolimus treatment has anti-inflammatory effects on AD skin as indicated by reduced infiltration of cytokine expressing inflammatory cells. No evidence for drug-induced systemic immunosuppression was obtained.