权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Relationship between sensitivities of peripheral blood-mononuclear cells to immunosuppressive drugs and Staphylococcus aureus infection

外周血单个核细胞对免疫抑制药物敏感性与金黄色葡萄球菌感染的关系

基本信息

批准号：
16590125
负责人：
HIRANO Toshihiko
金额：
$ 2.18万
依托单位：
Tokyo University of Pharmacy and Life Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Successful immunosuppressive therapy is critical for the treatment of organ transplant recipients and patients with autoimmune diseases. However, a considerable number of patients have shown clinical resistance to therapy. Bacterial infection might influence the clinical response of patients to immunosuppressive drugs, but few studies have been carried out to investigate the effect of bacterial superantigens on the efficacy of the drugs in these patients. We evaluated the suppressive efficacy of prednisolone, methylprednisolone, cyclosporine, and tacrolimus on the blastogenesis of PBMCs obtained from patients with chronic renal; failure renal awaiting transplantation, patients with several autoimmune diseases, and healthy subjects. In vitro drug concentrations giving 50% inhibition (IC_<50s>) of PBMC blastogenesis stimulated with concanavalin A (con A) or toxic shock syndrome toxin 1 (TSST-1) derived from Staphylocuccus aureus (S. aureus) were calculated. The ICσo values for the four drugs evaluated in TSST-1-stimulated PBMCs were significantly higher than those evaluated in con A-stimulated PBMCs (p<0.05). The amount of Interleukin 2 produced from PBMCs stimulated with TSST-1was significantly larger than that produced from PBMCs stimulated with con A in both patients and healthy subjects (p<0.05). These observations raise the possibility that TSST-1 induced by S. aureus infection attenuates the clinical efficacy of glucocorticoids and calcineurin inhibitors in patients with autoimmune diseases.

成功的免疫抑制治疗对器官移植受者和自身免疫性疾病患者的治疗至关重要。然而，相当数量的患者已经表现出临床上对治疗的抵抗。细菌感染可能会影响患者对免疫抑制药物的临床反应，但很少有人研究细菌超抗原对这些患者药物疗效的影响。我们评价了强的松龙、甲基强的松龙、环孢素和他克莫司对慢性肾功能衰竭患者、等待移植的肾功能衰竭患者、几种自身免疫性疾病患者和健康受试者外周血单核细胞转化的抑制效果。计算对刀豆蛋白A(ConA)或金黄色葡萄球菌中毒性休克综合征毒素1(TSST-1)刺激的PBMC增殖有50%抑制作用的药物浓度(IC50)。四种药物在TSST-1刺激的PBMC中的ICσo值显著高于ConA刺激的PBMC(p&lt；0.0 5)。TSST-1刺激的PBMC产生的IL-2显著高于ConA刺激的PBMC产生的IL-2(p&lt；0.05)。这些观察结果提出，金黄色葡萄球菌感染诱导的TSST-1可能会削弱糖皮质激素和钙调神经磷酸酶抑制剂在自身免疫性疾病患者中的临床疗效。