Comparative study of the effects of betamethasone butyrate propionate, vitamin D3 derivatives, and cyclosporine on human lymphocyte-proliferation stimulated with a hemolytic streptococci-derived superantigen
Comparative study of the effects of betamethasone butyrate propionate, vitamin D3 derivatives, and cyclosporine on human lymphocyte-proliferation stimulated with a hemolytic streptococci-derived superantigen
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DOI：
10.1016/j.ejphar.2007.06.023
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发表时间：
2007-10-01
影响因子：
5
通讯作者：
Hirano, Toshihiko
中科院分区：
文献类型：
--
作者：
Arai, Kae;Uchiyama, Terumi;Hirano, Toshihiko
细菌感染可能会影响包括银屑病在内的免疫性疾病患者对免疫抑制药物治疗效果的临床反应，但很少有研究探讨细菌超抗原的意义。我们评估了丁酸丙酸倍他米酯、维生素D-3衍生物和环孢霉素对刀豆球蛋白A或超抗原诱导的18例健康受试者外周血单核细胞增殖的抑制作用。在体外药物浓度给予50%的抑制（IC（50））的外周血单核细胞增殖刺激伴刀豆球蛋白A或链球菌热原肠毒素A进行了估计。用微珠阵列法测定外周血单个核细胞培养液中肿瘤坏死因子-α、干扰素-γ、白细胞介素-2、-4、-5或-40的浓度。在链球菌致热原肠毒素A刺激的外周血单核细胞中评价的丁酸丙酸倍他米酯的中位（范围）IC 50值为291.6（0.001-1171.5）ng/ml，显著高于伴刀豆球蛋白A刺激的外周血单核细胞中发现的值0.072（0.01-222.5）ng/ml（P=0.0245）。然而，卡泊三醇在链球菌致热原肠毒素A刺激的外周血单核细胞中的中位（范围）IC 50值为0.3（0.24-1357.4）ng/ml，显著低于伴刀豆球蛋白A刺激的外周血单核细胞中发现的值128.6（0.1-776.9）ng/ml（P=0.0323）。环孢霉素的IC 50值在伴刀豆球蛋白A和链球菌致热性肠毒素A刺激的PBMC之间没有显著差异。刀豆球蛋白A和链球菌致热原肠毒素A刺激的外周血单核细胞培养物之间的细胞因子浓度无显着差异。丁酸丙酸倍他米酯抑制这些细胞因子产生的作用比卡泊三醇强。溶血性链球菌定植诱导的链球菌致热性肠毒素A可减弱丁酸丙酸倍他米松的疗效。而卡泊三醇抑制链球菌的机制背景。虽然致热性肠毒素A诱导的外周血单核细胞增殖仍有待阐明，但维生素D-3衍生物似乎在抑制溶血性链球菌定殖患者的过敏性免疫中有效。(C)2007 Elsevier B. V.保留所有权利。
Bacterial infection might influence the clinical response of patients with immunological disorders including psoriasis to the therapeutic efficacies of immunosuppressive drugs, but few studies have been carried out to investigate the implication of bacterial superantigens. We evaluated the suppressive efficacies of betamethasone butyrate propionate, vitamin D-3 derivatives, and cyclosporine against concanavalin A- or superantigen-induced proliferation of peripheral-blood mononuclear cells obtained from 18 healthy subjects. In vitro drug concentrations giving 50% inhibition (IC(50)s) of peripheral-blood mononuclear cell-proliferation stimulated with concanavalin A or streptococcal pyrogenic enterotoxin A were estimated. Concentrations of tumor necrosis factor-alpha, interferon-gamma, interleukin-2, -4, -5, or 4 0, in a peripheral-blood mononuclear cell-culture medium were measured with beads-array procedures. The median (range) IC50 value for betamethasone butyrate propionate evaluated in the streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cells was 291.6 (0.001-1171.5) ng/ml, which was significantly higher than the value 0.072 (0.01-222.5) ng/ml found in concanavalin A-stimulated peripheral-blood mononuclear cells (P=0.0245). However, the median (range) IC50 value for calcipotriol in the streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cells was 0.3 (0.24-1357.4) ng/ml, which was significantly lower than the value 128.6 (0.1-776.9) ng/ml found in concanavalin A-stimulated peripheral-blood mononuclear cells (P=0.0323). The IC50 value for cyclosporine was not significantly different between the concanavalin A- and streptococcal pyrogenic enterotoxin A-stimulated PBMCs. Concentration for none of the cytokines was significantly different between concanavalin A- and streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cell cultures. The effects of betamethasone butyrate propionate to suppress these cytokine productions were rather stronger than those of calcipotriol. Streptococcal pyrogenic enterotoxin A induced by hemolytic streptococci colonization is suggested to attenuate the therapeutic efficacy of betamethasone butyrate propionate. While the mechanistic background of calcipotriol to suppress streptococcal. pyrogenic enterotoxin A-induced peripheral-blood mononuclear cell-proliferation remains to be elucidated, vitamin D-3 derivatives appears to be effective in suppressing anomalistic immunity in patients having hemolytic streptococci colonization. (C) 2007 Elsevier B.V. All rights reserved.