Lee P K, Deringer J R, Kreiswirth B N, Novick R P, Schlievert P M
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
Infect Immun. 1991 Mar;59(3):879-84. doi: 10.1128/iai.59.3.879-884.1991.
Toxic shock syndrome toxin 1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPE A) belong to a family of pyrogenic toxins produced by Staphylococcus aureus and Streptococcus pyogenes, respectively. Both toxins are responsible for causing toxic shock syndrome (TSS) and related illnesses, clinically characterized by multiorgan involvement. The most severe TSS symptom is acute hypotension and shock after the initial febrile response. In this study, we examined possible mechanisms of shock development in TSS, particularly the role of T-cell proliferation, endotoxin enhancement by toxins, and capillary leakage. American Dutch belted rabbits, with subcutaneously implanted miniosmotic pumps filled with either TSST-1 or SPE A, served as the animal model. For both TSST-1 and SPE A-treated rabbits, administration of cyclosporin A prevented toxin-induced T-cell proliferation but failed to protect the rabbits. Polymyxin B treatment of rabbits, to neutralize endogenous endotoxin, partially protected rabbits from challenge with either exotoxin; two of six rabbits survived on day 2 when treated with only TSST-1, whereas six of six animals survived after challenge with TSST-1 and polymyxin B. Similarly, with SPE A-treated rabbits, only 1 of 10 animals without polymyxin B treatment survived on day 8, but 4 of 6 rabbits survived on day 8 when given polymyxin B. Fluid replacement was successful in preventing lethality. Twelve of 14 rabbits survived when given TSST-1 with fluid, and all rabbits treated with SPE A and fluid survived. Finally, by using miniosmotic pumps, staphylococcal exfoliative toxin A and concanavalin A were administered to rabbits in an attempt to induce lethality. These two T-cell mitogens caused T-cell proliferation but failed to induce lethality in rabbits. The data suggest that toxin interactions causing vascular leakage and to some extent endotoxin enhancement are of major importance in development of hypotension and shock in TSS. It appears that T-cell proliferation may not contribute significantly to the induction of shock and death.
中毒性休克综合征毒素1（TSST-1）和链球菌致热外毒素A（SPE A）分别属于由金黄色葡萄球菌和化脓性链球菌产生的一类致热毒素。这两种毒素均会引发中毒性休克综合征（TSS）及相关疾病，其临床特征为多器官受累。TSS最严重的症状是在最初的发热反应后出现急性低血压和休克。在本研究中，我们探究了TSS中休克发展的可能机制，尤其是T细胞增殖、毒素对内毒素的增强作用以及毛细血管渗漏的作用。皮下植入填充有TSST-1或SPE A的微型渗透泵的美国荷兰带兔用作动物模型。对于TSST-1和SPE A处理的兔子，给予环孢素A可阻止毒素诱导的T细胞增殖，但未能保护兔子。用多粘菌素B处理兔子以中和内源性内毒素，可部分保护兔子免受任何一种外毒素的攻击；仅用TSST-1处理时，六只兔子中有两只在第2天存活，而在用TSST-1和多粘菌素B攻击后，六只动物全部存活。同样，对于SPE A处理的兔子，未用多粘菌素B处理的十只动物中只有一只在第8天存活，但给予多粘菌素B时，六只兔子中有四只在第8天存活。液体替代成功预防了致死性。给予TSST-1并补充液体时，十四只兔子中有十二只存活，所有用SPE A和液体处理的兔子均存活。最后，通过使用微型渗透泵，将葡萄球菌剥脱毒素A和伴刀豆球蛋白A给予兔子以试图诱导致死性。这两种T细胞有丝分裂原引起T细胞增殖，但未能在兔子中诱导致死性。数据表明，导致血管渗漏以及在一定程度上增强内毒素的毒素相互作用在TSS中低血压和休克的发展中起主要作用。看来T细胞增殖可能对休克和死亡的诱导作用不大。
