THE EFFECT OF CYTOTOXIC AGENTS ON THE PRIMARY IMMUNE RESPONSE TO LISTERIA MONOCYTOGENES
THE EFFECT OF CYTOTOXIC AGENTS ON THE PRIMARY IMMUNE RESPONSE TO LISTERIA MONOCYTOGENES
复制标题
细胞毒药物对单核细胞增生李斯特氏菌初次免疫反应的影响
DOI：
--
复制
发表时间：
1969
影响因子：
15.3
通讯作者：
G. Mackaness
中科院分区：
文献类型：
--
作者：
S. Tripathy;G. Mackaness
研究了四种不同类型的细胞毒性药物对小鼠李斯特菌感染免疫反应的影响。宿主免疫反应的发展通过脾脏和肝脏细菌生长曲线斜率的渐进式变化来揭示。在未治疗的小鼠中24小时发病，但在有效的免疫抑制作用下，生物体不间断地繁殖，直到动物因严重感染而死亡。在感染时单次注射环磷酰胺、长春碱和硫唑嘌呤均产生有效的免疫抑制作用，其特征是细菌持续繁殖。甲氨蝶呤也有免疫抑制作用，但与其他药物不同，它的作用是可逆的。然而，通过进一步治疗，它们可以维持下去。对时间反应关系的研究表明，环磷酰胺在感染前2天至感染后4天的广泛时间跨度内具有高度活性。另一方面，长春花碱在感染当天给予的作用最大，而甲氨蝶呤在感染后48小时给予的作用最大。这些差异表明这三种药物作用于参与宿主免疫反应的不同细胞群。所观察到的效果已与所测药物的已知作用方式进行了讨论。在感染前7-11天使用环磷酰胺或长春花碱，在感染前4天使用甲氨蝶呤，观察到免疫增强的现象；停药后淋巴组织的反应性增生再次被提出作为这种矛盾效应发生的解释。所采用的实验模型很简单，只需要常规的细菌学设施和最少的设备。它似乎为评估药物的免疫抑制活性和确定其作用的时间过程提供了一种有用的方法；它在筛选抗癌药物方面也有价值。
Four drugs, representing four different categories of cytotoxic agents, were studied for their effect on the immune response to Listeria infection in mice. The development of the host's immune response is revealed by a progressive change in the slope of the bacterial growth curve in spleen and liver. It has its onset at 24 hr in untreated mice, but in the presence of effective immunosuppression the organism multiples uninterruptedly until the animal dies from overwhelming infection. When administered as single injections at the time of infection, cyclophosphamide, vinblastine, and azathioprine all produced an effective immunosuppression, characterized by continuous bacterial multiplication. Methotrexate was also immunosuppressive, but unlike the others its effects were reversible. They could be sustained, however, by further treatment. Studies of the time-response relationship indicated that cyclophosphamide was highly active over a broad time-span ranging from 2 days before infection to 4 days after infection. Vinblastine on the other hand was maximally active when given on the day of infection, while methotrexate had its greatest effect when given 48 hr after infection. These differences indicate that these three drugs act on different cell populations involved in the host's immune response. The effects observed have been discussed in relation to what is known of the modes of action of the drugs tested. An observation of interest was the phenomenon of enhanced immunity in animals treated with cyclophosphamide or vinblastine 7–11 days before, and with methotrexate 4 days before infection; reactive hyperplasia of lymphoid tissue following withdrawal of drug was again advanced as an explanation for the occurrence of this paradoxical effect. The experimental model employed is simple, requiring only routine bacteriological facilities and minimal equipment. It seems to offer a useful means of assessing the immunosuppressive activity of drugs and of determining the time-course of their action; it could also be of value in the screening of anticancer agents.