title: Evaluation of beneficial and adverse effects of glucocorticoids on a newly developed full-thickness skin model.
abstract: Glucocorticoids (GCs) are highly effective compounds widely used in the treatment of inflammatory diseases; however, they offer distinct adverse effects such as skin thinning in response to long-term topical treatment. Nevertheless it is difficult to deduce the safety of a newly synthesized compound from its structural formula. Efficient assay systems that measure beneficial and adverse effects are needed. In the present study the applicability of a three-dimensional full-thickness skin model (FTSM) is tested to display GC-induced effects regarding anti-inflammation and atrophy. It is shown that topical application of a commercial GC ointment suppresses the ultraviolet (UV)B induced induction of interleukin (IL)-6 and IL-8. Addition of purified betamethasone-17-valerate, prednicarbate and clobetasol-17-propionate to the culture medium for 14 days caused a reduction in the number of epidermal cell-layers corresponding to the atrophic risk found in vivo. Similarly, repeated topical application of five GC creams induced epidermal thinning. Evidence is given that the inhibitory effect on keratinocyte proliferation contributes to this effect. Furthermore, dermal thinning was monitored by measuring type I collagen synthesis; a decreased collagen synthesis similar to the in vivo situation is shown. The present study demonstrates the versatility of this FTSM in the validation of effectiveness and safety of GCs.
authors.affiliation: Department of Dermatology and Venerology, J.W. Goethe-University, Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
authors.forename: Nadja Nicole
authors.initials: NN
authors.lastname: Zöller
authors.forename: Stefan
authors.initials: S
authors.lastname: Kippenberger
authors.forename: Diamant
authors.initials: D
authors.lastname: Thaçi
authors.forename: Karsten
authors.initials: K
authors.lastname: Mewes
authors.forename: Martina
authors.initials: M
authors.lastname: Spiegel
authors.forename: Andrea
authors.initials: A
authors.lastname: Sättler
authors.forename: Maike
authors.initials: M
authors.lastname: Schultz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bereiter-Hahn
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: August
authors.initials: A
authors.lastname: Bernd
mesh_terms: D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D049109:Cell Proliferation / Q000187:drug effects; D002675:Child, Preschool; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology* / Q000633:toxicity*; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D009824:Ointments; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D016209:Interleukin-8; D009824:Ointments; D003094:Collagen