Pimecrolimus leads to an apoptosis-induced depletion of T cells but not Langerhans cells in patients with atopic dermatitis

Apart from the long-used corticosteroids, topical calcineurin inhibitors (tacrolimus, pimecrolimus) represent novel therapeutic options for the treatment of atopic dermatitis. This study was designed to investigate the pathophysiological target cells and mode of action of pimecrolimus in atopic skin...

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Bibliographic Details
Published in:Journal of Allergy and Clinical Immunology 2005-06, Vol.115 (6), p.1276-1283
Main Authors: Hoetzenecker, Wolfram, Ecker, Rupert, Kopp, Tamara, Stuetz, Anton, Stingl, Georg, Elbe-Bürger, Adelheid
Format: Article
Language:English
Subjects:
Administration, Topical
Adolescent
Adult
Allergic diseases
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Apoptosis
Atopic dermatitis
Biological and medical sciences
Cell Division
corticosteroids
Dermatitis
Dermatitis, Atopic - drug therapy
Dermatitis, Atopic - immunology
Double-Blind Method
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immune system
Immunopathology
Langerhans cells
Langerhans Cells - drug effects
Langerhans Cells - physiology
Male
Medical research
Medical sciences
Middle Aged
pimecrolimus
Skin - drug effects
Skin - immunology
Skin allergic diseases. Stinging insect allergies
T cells
T-Lymphocytes - drug effects
T-Lymphocytes - physiology
Tacrolimus - administration & dosage
Tacrolimus - analogs & derivatives
Tacrolimus - therapeutic use
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Summary:Apart from the long-used corticosteroids, topical calcineurin inhibitors (tacrolimus, pimecrolimus) represent novel therapeutic options for the treatment of atopic dermatitis. This study was designed to investigate the pathophysiological target cells and mode of action of pimecrolimus in atopic skin. Twenty-two patients were randomly assigned to treatment with pimecrolimus cream 1%, matching vehicle cream, or β-methasone-17-valerate (BMV) cream 0.1% in a randomized, double-blind, vehicle-controlled, parallel group clinical trial. Treatment was given twice daily for 3 weeks. Cryostat sections of skin biopsies were taken before as well as at selected time points after initiation of therapy. For certain experiments, healthy volunteers were topically treated with the creams described twice a day on 5 consecutive days. Epidermal sheets were prepared from suction blisters. For in vitro experiments, untreated, healthy human skin was obtained from patients undergoing plastic surgery. The effect of pimecrolimus and BMV on Langerhans cells (LCs), inflammatory dendritic epidermal cells, and T cells was investigated by using immunofluorescence and flow-cytometry techniques. While topical BMV treatment depleted LCs in healthy and atopic skin, pimecrolimus did not affect their number. Correlating with the disappearance of inflammatory cells, we observed a depletion of inflammatory dendritic epidermal cells and T cells on pimecrolimus and BMV treatment. Furthermore, we show that pimecrolimus depletes T cells by the induction of apoptosis. In summary, our data show that pimecrolimus reduces pathological T cells in atopic dermatitis skin via apoptosis, whereas LCs remain unaffected.
ISSN:0091-6749
1097-6825
1365-2567
DOI:10.1016/j.jaci.2005.02.011