title: Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis Relies on Suppression of the Inflammatory TNFα - IL-23 - IL-17 Axis.
abstract: The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T-cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/betamethasone, but not by betamethasone. Immunohistochemical analysis revealed that calcipotriol/betamethasone reduced the numbers of CD4+ and CD8+ T cells and Tregs in psoriatic lesions more than betamethasone. Flow cytometric analyses demonstrated that calcipotriol/betamethasone decreased the numbers of circulating CD8+ T cells, Tregs, skin-homing Th17 memory cells and Th22 memory cells, while betamethasone had little or no effect. Glucocorticoid receptors GRα and GRß were expressed in psoriatic skin. In conclusion, calcipotriol increases the immunosuppressive power of betamethasone by suppressing the inflammatory TNF-α - IL-23 - IL-17 axis.
authors.affiliation: PEDEGO Research Unit, Oulu Center for Cell-Matrix Research, Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90029 Oulu, Finland. minna.kubin@ppshp.fi.
authors.forename: Minna E
authors.initials: ME
authors.lastname: Kubin
authors.forename: Nina
authors.initials: N
authors.lastname: Kokkonen
authors.forename: Riitta
authors.initials: R
authors.lastname: Palatsi
authors.forename: Päivi M
authors.initials: PM
authors.lastname: Hägg
authors.forename: Juha P
authors.initials: JP
authors.lastname: Väyrynen
authors.forename: Virpi
authors.initials: V
authors.lastname: Glumoff
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.forename: Tiina
authors.initials: T
authors.lastname: Hurskainen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Tasanen
mesh_terms: D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001623:Betamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004338:Drug Combinations; D005387:Finland; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; C517164:betamethasone dipropionate, calcipotriol drug combination; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D001623:Betamethasone; D002117:Calcitriol