Original Article
Subject Category: Immunology/Infection
Journal of Investigative Dermatology (2009) 129, 2184–2192; doi:10.1038/jid.2009.50; published online 19 March 2009
Differential Effects of Corticosteroids and Pimecrolimus on the Developing Skin Immune System in Humans and Mice
Simone Meindl1, Christine Vaculik1, Josef G Meingassner2, Gero Kramer3, Johnnie Akgün1, Marion Prior1, Anton Stuetz2, Georg Stingl1 and Adelheid Elbe-Bürger1
- 1Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Vienna Competence Center, Medical University of Vienna, Vienna, Austria
- 2Novartis Institutes for BioMedical Research, Vienna, Austria
- 3Department of Urology, Medical University of Vienna, Austria
Correspondence: Dr Adelheid Elbe-Bürger, Division of Immunology, Allergy and Infectious Diseases, Vienna Competence Center, Department of Dermatology, Medical University of Vienna, Lazarettgasse 19, Vienna A-1090, Austria. E-mail: adelheid.elbe-buerger@meduniwien.ac.at
Received 19 August 2008; Revised 19 December 2008; Accepted 25 January 2009; Published online 19 March 2009.
Abstract
Atopic dermatitis arises primarily in early infancy. In these patients, corticosteroids are used especially with great caution because of their side effects. Calcineurin inhibitors such as pimecrolimus (PIM) could be useful, but safety concerns have been raised in particular because of the lack of knowledge about their effects on the developing skin immune system. This study was designed to investigate the impact of PIM and corticosteroids on epidermal cells (EC) in infants and newborn mice. We found that the percentage of unfractionated viable infant ECs was significantly decreased in the presence of
-methasone-17-valerate (BMV) but not PIM. Exposure of unfractionated infant ECs to BMV but not to PIM and vehicle control caused a significant inhibition of the upregulation of CD86 molecules on Langerhans cells (LC). The release of cytokines by LCs and ECs, cultured in the presence of BMV and PIM, was not significantly reduced compared with controls. Topical corticosteroid but not PIM application onto newborn mice induced apoptosis in some LC precursors. Our data suggest that similar to the situation in adult skin, corticosteroids may impair LC maturation as well as viability of ECs in infants, effects not seen with PIM.
Abbreviations:
BMV,
-methasone-17-valerate; CLO, clobetasole-17-propionate; CLSM, confocal laser scanning microscope; DC, dendritic cell; EC, epidermal cell; GR, glucocorticoid receptor; LC, Langerhans cell; MACS, magnetic-activated cell sorting; MCP-1, monocyte chemotactic protein-1; PE, phycoerythrin; PIM, pimecrolimus; TNF-
, tumor necrosis factor-
; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
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