Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.
Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.
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DOI：
10.1371/journal.pone.0053078
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Thaunat O
中科院分区：
文献类型：
--
作者：
Buron F;Malvezzi P;Villar E;Chauvet C;Janbon B;Denis L;Brunet M;Daoud S;Cahen R;Pouteil-Noble C;Gagnieu MC;Bienvenu J;Bayle F;Morelon E;Thaunat O
免疫抑制剂西罗莫司在肾移植中的使用已成为问题，因为频繁发生各种副作用，包括反常的炎症表现，其病理生理学仍然难以捉摸。对30名需要从钙调磷酸酶抑制剂转换为西罗莫司免疫抑制剂的肾移植受者进行了3个月的前瞻性随访。使用视觉模拟量表对患者的炎症症状进行量化，并在转换前、转换后15、30和90天收集血清样本。66%的患者报告了至少1种炎症症状，皮肤粘膜表现是最常见的。炎症症状的特点是其不稳定性和随机性，每个病人表现出独特的临床表现。生化特征更均匀，血红蛋白下降，同时炎症急性期蛋白升高，在转换后1个月血清中达到峰值。分析西罗莫司引入对细胞因子微环境的影响，我们观察到IL 6和TNFα的增加，而没有依赖于IL 10和可溶性TNF受体的负反馈环的补偿。IL 6和TNFα的变化与生化和临床炎症表现的强度在线性回归模型中相关。西罗莫司引发移植患者中炎性细胞因子平衡的不稳定，其促进矛盾的炎性反应，在药物引入后的数周内具有轻度随机临床症状。这种病理生理机制将西罗莫司反复报告的各种个体炎症副作用统一起来，表明它们应被视为单一综合征实体。
The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive. 30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch. 66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNFα without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNFα changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model. Sirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.
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影响因子：
6.2
作者：
Segundo, David San;Ruiz, Juan Carlos;Arias, Manuel
通讯作者：
Arias, Manuel
影响因子：
6.2
作者：
Maiorano, Annamaria;Stallone, Giovanni;Grandaliano, Giuseppe
通讯作者：
Grandaliano, Giuseppe
影响因子：
8.8
作者：
Brouard, S.;Puig-Pey, I.;Sanchez-Fueyo, A.
通讯作者：
Sanchez-Fueyo, A.
影响因子：
8.8
作者：
Gao, W.;Lu, Y.;Strom, T. B.
通讯作者：
Strom, T. B.
影响因子：
15.9
作者：
Nicolas, G;Chauvet, C;Vaulont, S
通讯作者：
Vaulont, S