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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Paradoxes of immunosuppression in mouse models of withdrawal.
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Paradoxes of immunosuppression in mouse models of withdrawal.

机译：戒断小鼠模型中免疫抑制的悖论。

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Previously, our laboratory showed that either abrupt (AW) or precipitated withdrawal (PW) from morphine led to profound suppression of murine splenic antibody responses to sheep red blood cells at 24 h post-withdrawal. In the present studies, we examined the immune mechanisms mediating suppression at that time point. A co-culture method was used to examine whether cells from withdrawn mice had (1) a deficit in function and/or (2) contained populations of suppressor cells. To examine the first hypothesis, cells from normal mice were co-cultured with cells from withdrawn mice in a 1:3 ratio (normal/withdrawn). To test the second hypothesis, the ratio was reversed. The results were paradoxical. Co-culture of cells in a 1:3 ratio showed that spleen cells from withdrawn mice had a deficit in macrophage function. Spleen cells from withdrawn mice also showed decreased mRNA levels of IL-1beta, IL-1-Ra, and TNF-alpha and a suppression of co-stimulatory molecule expression. To examine the second hypothesis, cells were co-cultured in a 3:1 ratio (normal/withdrawn). In this paradigm, spleen cells from abrupt withdrawn mice were shown to contain populations of both suppressor macrophages and B-cells. In vivo experiments carried out on mice 24 h post-withdrawal showed increased sensitivity to the lethal effects of LPS and increased production of TNF-alpha, implying a state of macrophage activation. Thus evidence for both suppressed and activated macrophages has been obtained in mice 24 h after abrupt withdrawal from morphine.
机译：以前，我们的实验室表明，在退出后24小时，从吗啡突然（AW）或沉淀的退出（PW）会导致小鼠脾脏抗体对绵羊红细胞的强烈抑制。在本研究中，我们研究了在那个时间点介导抑制的免疫机制。使用共培养方法检查退出小鼠的细胞是否具有（1）功能缺陷和/或（2）抑制细胞群。为了检验第一个假设，将正常小鼠的细胞与撤回小鼠的细胞以1：3的比例（正常/撤回）进行共培养。为了检验第二个假设，将比率颠倒了。结果是矛盾的。以1：3的比例共培养细胞表明，撤回小鼠的脾细胞在巨噬细胞功能方面存在缺陷。撤离小鼠的脾细胞还显示IL-1beta，IL-1-Ra和TNF-α的mRNA水平降低，并且共刺激分子表达受到抑制。为了检验第二种假设，将细胞以3：1的比例共培养（正常/撤回）。在这种范例中，突然撤离的小鼠的脾细胞显示出同时含有抑制性巨噬细胞和B细胞。撤离后24小时对小鼠进行的体内实验表明，对LPS致死作用的敏感性增加，TNF-α的产生增加，这表明巨噬细胞处于激活状态。因此，从吗啡突然撤药后24小时，已经在小鼠体内获得了抑制和活化的巨噬细胞的证据。

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