Miethke T, Duschek K, Wahl C, Heeg K, Wagner H
Institute of Medical Microbiology and Hygiene Technical University of Munich, FRG.
Eur J Immunol. 1993 Jul;23(7):1494-500. doi: 10.1002/eji.1830230715.
The pathogenesis of the toxic shock syndrome (TSS) is only incompletely understood. We now present evidence that TSS toxin-1 (TSST-1), one of the superantigens produced by Staphylococcus aureus, induces lethal shock in D-galactosamine sensitized mice. In this model TSS is dependent on T cells, since cyclosporin A (CsA) completely blocked development of shock, and since T cell-deficient SCID mice did not show signs of disease upon injection with TSST-1. However, SCID mice repopulated with T cells succumbed to lethal shock. The disease is characterized by a burst of lymphokines like interleukin-2 (IL-2) and tumor necrosis factor (TNF) released into the sera of TSST-1-treated animals. Already 1-2 h after TSST-1 application TNF serum levels peaked and IL-2 levels peaked around 4 h after treatment. TNF appears as key mediator of TSS, because anti-TNF monoclonal antibodies protected TSST-1-challenged mice. Interestingly, the burst of TNF in serum was noted well in advance of detectable markers of T cell activation. Thus, about 5% of all peripheral T cells started to express the IL-2 receptors as late as 4 h after treatment. Comparing TSST-1- and endotoxin-induced shock we conclude that TNF effects shock in both diseases. However, the type of cells involved appears distinct in that T cells cause TSS triggered by the exotosin TSST-1 while macrophages mediate the shock induced by endotoxins.
中毒性休克综合征（TSS）的发病机制目前仅得到部分了解。我们现在提供证据表明，金黄色葡萄球菌产生的超抗原之一——TSS毒素-1（TSST-1），可在D-半乳糖胺致敏的小鼠中诱发致死性休克。在该模型中，TSS依赖于T细胞，因为环孢素A（CsA）可完全阻断休克的发展，而且T细胞缺陷的SCID小鼠在注射TSST-1后未表现出疾病迹象。然而，重新植入T细胞的SCID小鼠会死于致死性休克。该疾病的特征是，在接受TSST-1治疗的动物血清中会突然释放出大量细胞因子，如白细胞介素-2（IL-2）和肿瘤坏死因子（TNF）。在应用TSST-1后1-2小时，TNF血清水平即达到峰值，而IL-2水平在治疗后约4小时达到峰值。TNF似乎是TSS的关键介质，因为抗TNF单克隆抗体可保护受到TSST-1攻击的小鼠。有趣的是，血清中TNF的突然升高早在T细胞活化的可检测标志物出现之前就已被注意到。因此，直到治疗后4小时，所有外周T细胞中约5%才开始表达IL-2受体。比较TSST-1和内毒素诱发的休克，我们得出结论，TNF在这两种疾病中均会引发休克。然而，所涉及的细胞类型似乎有所不同，T细胞会引发由外毒素TSST-1触发的TSS，而巨噬细胞则介导由内毒素诱发的休克。
