Yamazaki Kyosuke, Kiyomi Anna, Imai Shinobu, Sugiura Munetoshi
Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Evid Based Complement Alternat Med. 2022 Feb 28;2022:9738989. doi: 10.1155/2022/9738989. eCollection 2022.
Prednisolone (PSL), a type of corticosteroid used to treat autoimmune diseases, can increase the risk of infection and osteoporosis. Saireito (114), a Kampo medicine, has an immunosuppressive effect; with its use, the dose of steroids can be reduced. However, its mechanism when used with PSL is still unclear. We used peripheral blood mononuclear cells (PBMCs) from healthy adults to examine the effect of 114 and PSL treatment on PBMC proliferation, T-cell subsets, and cytokine production. PBMCs were cotreated with concanavalin A and 300 M 114 (either Tsumura & Co. (TJ) or Kracie Holdings (KR)) and 0.0001-1.0 M PSL for 96 h to create the T-cell mitogen. We then measured the PBMC proliferation; ratio of CD4 T cells, CD8 T cells, and T-follicular helper (Tfh) cells; and concentration of cytokines (TNF, IFN-, IL-6, IL-10, IL-17A, and IL-21). The proliferation of PBMCs was dose dependently suppressed in both the PSL and PSL + 114 groups (p < 0.05). Combination therapy increased the IC in the PSL group (0.0947 M) by 2.02 and 1.64-fold in the PSL + TJ114 and PSL + KR114 groups, respectively. Both the PSL + 114 groups had an increased ratio of CD4 T cells compared to the PSL group, with no effect on the ratio of CD8 T and Tfh cells. Furthermore, the PSL + 114 groups showed increased IL-6 and IL-10 compared to the PSL monotherapy group, although the difference was not significant. There was no significant difference in the TNF, IFN-, IL-17A, and IL-21 concentrations between the PSL and PSL + 114 groups. The elevated IC with 114 cotreatment suggests diminished immunosuppressive action. Moreover, increased cytokine production by Th2 with 114 cotreatment suggests a restoration of T-cell balance in Th1-mediated autoimmune diseases. However, increased IL-6 suggests potential exacerbation of IL-6-mediated diseases, such as rheumatoid arthritis. Therefore, it is necessary to monitor these clinical parameters when using 114 in combination with PSL.
泼尼松龙（PSL）是一种用于治疗自身免疫性疾病的皮质类固醇，会增加感染风险和骨质疏松症的风险。柴苓汤（114）是一种汉方药，具有免疫抑制作用；使用它可以减少类固醇的剂量。然而，其与PSL联合使用时的机制仍不清楚。我们使用健康成年人的外周血单个核细胞（PBMC）来研究114和PSL治疗对PBMC增殖、T细胞亚群和细胞因子产生的影响。将PBMC与伴刀豆球蛋白A以及300μM的114（津村株式会社（TJ）或佳丽宝控股（KR）生产）和0.0001 - 1.0μM的PSL共同处理96小时，以产生T细胞有丝分裂原。然后我们测量了PBMC增殖；CD4 T细胞、CD8 T细胞和滤泡辅助性T细胞（Tfh）的比例；以及细胞因子（TNF、IFN - 、IL - 6、IL - 10、IL - 17A和IL - 21）的浓度。在PSL组和PSL + 114组中，PBMC的增殖均呈剂量依赖性受到抑制（p < 0.05）。联合治疗使PSL组（0.0947μM）的半数抑制浓度（IC）在PSL + TJ114组和PSL + KR114组中分别增加了2.02倍和1.64倍。与PSL组相比，两个PSL + 114组的CD4 T细胞比例均增加，而对CD8 T细胞和Tfh细胞的比例没有影响。此外，与PSL单药治疗组相比，PSL + 114组的IL - 6和IL - 10有所增加，尽管差异不显著。PSL组和PSL + 114组之间的TNF、IFN - 、IL - 17A和IL - 21浓度没有显著差异。与114共同处理后IC升高表明免疫抑制作用减弱。此外，与114共同处理后Th2细胞因子产生增加表明在Th1介导的自身免疫性疾病中T细胞平衡得到恢复。然而，IL - 6增加表明可能会加重IL - 6介导的疾病，如类风湿性关节炎。因此，在将114与PSL联合使用时，有必要监测这些临床参数。
