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

• Published in: Journal of Allergy and Clinical Immunology Vol. 115; no. 6; pp. 1276 - 1283
• Main Authors: Hoetzenecker, Wolfram, Ecker, Rupert, Kopp, Tamara, Stuetz, Anton, Stingl, Georg, Elbe-Bürger, Adelheid
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-06-2005; Elsevier; Elsevier Limited
• 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; AD; apoptosis; EMP; BMV; T cells; pimecrolimus; EASI; FITC; TUNEL; corticosteroids; APC; Atopic dermatitis; PE; LC; Langerhans cells; IDEC; CLSM; EC; DC; Human; Allergy; Immunopathology; Skin disease; Pimecrolimus; Macrolide; Atopy; Immunology; Depletion; Langerhans cell; Antigen presenting cell; Cell death; T-Lymphocyte; Mechanism of action; Apoptosis
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2005.02.011

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.