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

成功的免疫抑制治疗对于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，相当多的患者已经显示出对治疗的临床抗性。细菌感染可能会影响患者对免疫抑制药物的临床反应，但很少有研究调查细菌超抗原对这些患者的药物疗效的影响。我们评估了泼尼松龙、甲基泼尼松龙、环孢菌素和他克莫司对从慢性肾衰竭患者、等待移植的肾衰竭患者、患有多种自身免疫性疾病的患者和健康受试者中获得的PBMCs胚细胞发生的抑制作用。对<50s>用伴刀豆球蛋白A（con A）或来源于金黄色葡萄球菌（S.金黄色葡萄球菌）。在TSST-1刺激的PBMC中评估的四种药物的ICσ 0值显著高于在con A刺激的PBMC中评估的IC σ 0值（p&lt;0.05）。TSST-1刺激PBMC产生IL-2的量显著高于Con A刺激PBMC产生IL-2的量（p&lt;0.05）。这些结果提示TSST-1可能是由S.金黄色葡萄球菌感染减弱了糖皮质激素和钙调磷酸酶抑制剂在自身免疫性疾病患者中的临床疗效。

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.