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.

Inhibition of IL-17–committed T cells in a murine psoriasis model by a vitamin D analogue

“…40,41 Thus it is theoretically possible that the antipsoriatic effects of topical vitamin D analogues might be due in part to their effects on immune cells. In fact, several studies 42,43 indirectly imply a possible inhibitory effect of topical vitamin D analogues on IL-23 and IL-17A expression in lesional skin of patients with psoriasis; however, it has not yet been clearly shown whether topical vitamin D analogues actually control the immune pathogenesis of psoriasis in vivo. In addition, topical vitamin D analogues are generally regarded as local symptomatic treatments, and their effects on the systemic pathogenesis of psoriasis remain to be addressed.…”

Ten-eleven Translocation-2 Regulates DNA Hydroxymethylation Status and Psoriasiform Dermatitis Progression in Mice

“…IL-17 can activate various immune cells to produce a variety of cytokines and chemokines, and stimulates the production of antimicrobial peptides that promote recruitment of inflammatory cells (27). The pathogenic mechanisms of psoriasis are critically dependent on the IL-23/IL-17 axis (28). The lineage-specific transcription factors T-bet and RORγt are key regulators of Th1 and Th17 cell function, respectively.…”

Glucocorticoids: The mode of action in bullous pemphigoid

“…In the study by Le Jan et al, super potent topical GCs reduced both IL‐17 expression and clinical symptoms of BP without decreasing serum autoantibody concentration rapidly in few days. Rapid reduction of IL‐17 expression has also been shown in psoriatic patients treated with potent topical GCs …”