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In vitro pyrogenicity of the diphtheria, tetanus and acellular pertussis components of a trivalent vaccine

机译:三价疫苗的白喉,破伤风和无细胞百日咳成分的体外热原性

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We have earlier found that a trivalent vaccine, containing antigenic components from both Gram-positive and Gram-negative bacteria, induced secretion of the endogenous pyrogen interleukin 6 (IL-6) when added to fresh human blood in vitro. The results of the present study showed that the IL-6 secretion was induced by toxoids derived from the Gram-positive bacterium Corynebacterium diphtheriae. However, fresh whole blood from different donors reacted differently to the stimulation. The blood from some donors induced secretion of large concentrations of IL-6, while the blood from other donors induced essentially no IL-6 secretion as a response to stimulation with diphtheria toxoid or a mixture of diphtheria and tetanus toxoids. Repeated testing over several years using blood from the same donor confirmed a donor-dependency of the reaction. This donor-dependency was only found for the toxoid, since blood from all donors reacted with approximately similar IL-6 production to stimulation by endotoxin from the Gram-negative bacterium Escherichia coli, known to be mediated via the toll-like receptor (TLR) 4. Also, no donor-dependecy was found to highly purified lipoteichoic acid from the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, known to be mediated via TLR-2 and TLR-6. The receptors involved in stimulation by diphtheria toxoid are not known, but may differ from those used by endotoxin and lipoteichoic acid.
机译:我们较早地发现,含有来自革兰氏阳性和革兰氏阴性细菌的抗原成分的三价疫苗,当将其添加到体外新鲜人类血液中时,会诱导内源性致热原白介素6(IL-6)的分泌。本研究结果表明,IL-6分泌是由革兰氏阳性细菌白喉棒状杆菌衍生的类毒素诱导的。但是,来自不同供体的新鲜全血对刺激的反应不同。来自一些供体的血液诱导分泌大量的IL-6,而来自其他供体的血液则基本上不诱导IL-6分泌,这是对白喉类毒素或白喉和破伤风类毒素混合物刺激的反应。使用来自同一供体的血液进行了数年的重复测试,证实了该反应对供体的依赖性。这种供体依赖性仅针对类毒素,因为所有供体的血液产生的IL-6产生的反应与革兰氏阴性细菌大肠杆菌的内毒素刺激产生的反应大致相似,已知这种细菌是通过通行费样受体(TLR)介导的4.另外,未发现供体依赖于革兰氏阳性细菌枯草芽孢杆菌和金黄色葡萄球菌的高纯度脂磷壁酸,已知这是通过TLR-2和TLR-6介导的。尚不知道白喉类毒素刺激所涉及的受体,但可能与内毒素和脂磷壁酸所使用的受体不同。

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