Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan.
Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
Molecules. 2020 Apr 16;25(8):1822. doi: 10.3390/molecules25081822.
Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients' lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4 T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.
中重度银屑病是一种免疫介导的炎症性疾病，会对患者的生活造成负面影响。环孢素 A（CsA）是一种有效的免疫调节剂，用于治疗银屑病。CsA 低剂量无效，高剂量有毒。阿卡波糖（Acar）是一种常用的具有抗炎和免疫调节作用的抗糖尿病药物，可降低咪喹莫特（IMQ）诱导的银屑病严重程度。与高剂量单一药物相比，联合使用全身药物通常更有效且更安全。我们观察到，与单独使用 Acar（250mg/kg）、低剂量 CsA（10 或 20mg/kg）或 IMQ 相比，用 Acar（250mg/kg）和低剂量 CsA（10 或 20mg/kg）联合治疗的小鼠表现出明显更轻微的 IMQ 诱导的银屑病样皮炎和更光滑的背部皮肤。与 Acar、低剂量 CsA 和 IMQ 单独使用相比，联合治疗显著降低了血清和皮肤中 Th17 相关细胞因子（白细胞介素（IL）-17A、IL-22 和 IL-23）和 Th1 相关细胞因子肿瘤坏死因子-α（TNF-α）的水平。此外，联合治疗还显著降低了产生 IL-17 和 IL-22 的 CD4 T 细胞（分别为 Th17 和 Th22 细胞）的比例，并增加了 Treg 细胞的比例。我们的数据表明，Acar 和低剂量 CsA 的联合治疗通过抑制炎症缓解银屑病皮肤损伤。这些发现为免疫调节药物在银屑病治疗中的作用提供了新的见解。
