Work

Combined Maxacalcitol/Betamethasone Butyrate Propionate Ointment Possesses Long‐Term Sustained Effects of Inducing Regulatory T Cells and Downregulating the Th17 Response, Even After Discontinuation of Its Application in Imiquimod‐Induced Psoriasiform Dermatitis

Year: 2025

Type: article

Abstract: ABSTRACT We often experience sustained improvement, even after discontinuation of treatment in psoriasis lesions treated with topical vitamin D 3 (VD 3 ) or the combination of topical corticosteroids and VD 3 . However, the underlying mechanisms of these sustained effects remain unclear. We explored mechanisms for the sustained effects of maxacalcitol (MCT) and combined MCT/betamethasone butyrate propionate (BBP) ointments using a murine psoriasiform dermatitis model induced by imiquimod (IMQ). IMQ was applied once daily to the shaved backs of mice for 6 days to induce psoriasiform dermatitis. MCT, BBP, combined MCT/BBP ointment, or their vehicles were treated for 3 days prior to IMQ application. IMQ was reapplied after 1, 2, or 3 weeks from the first IMQ application to investigate the sustained effects of their ointments. In the first application of IMQ, the administration of MCT, BBP, or MCT/BBP ointment improved clinical and pathological manifestations and reduced Th17‐related cytokines. Treatment with MCT or MCT/BBP showed an increase in IL‐10 mRNA expression and a higher count of Foxp3 + cells within the skin, but not in those with BBP. The induction of IL‐10 by MCT and MCT/BBP persisted until reapplication of IMQ 2 weeks later, although their effects diminished 3 weeks later. The reduction in Th17‐related cytokines was maintained up to 3 weeks later in MCT/BBP, whereas it was not observed 2 weeks later in MCT. In conclusion, MCT and MCT/BBP showed long‐term effects by induction of regulatory T cells and IL‐10. Additionally, MCT/BBP downregulated Th17‐related cytokines, which could contribute to the sustained improvement after discontinuation observed in clinical practice.

Source: The Journal of Dermatology

DOI: 10.1111/1346-8138.70031