title: Differential effects of corticosteroids and pimecrolimus on the developing skin immune system in humans and mice.
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 beta-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.
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Vienna Competence Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Meindl
authors.forename: Christine
authors.initials: C
authors.lastname: Vaculik
authors.forename: Josef G
authors.initials: JG
authors.lastname: Meingassner
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.forename: Johnnie
authors.initials: J
authors.lastname: Akgün
authors.forename: Marion
authors.initials: M
authors.lastname: Prior
authors.forename: Anton
authors.initials: A
authors.lastname: Stuetz
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.forename: Adelheid
authors.initials: A
authors.lastname: Elbe-Bürger
mesh_terms: D000305:Adrenal Cortex Hormones / Q000633:toxicity*; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001624:Betamethasone Valerate / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013234:Stem Cells / Q000187:drug effects; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; C117268:pimecrolimus; D001624:Betamethasone Valerate; D016559:Tacrolimus