MODIFICATION OF THE MURINE IMMUNE-SYSTEM BY GLUCOCORTICOSTEROIDS - ALTERATIONS OF THE TISSUE LOCALIZATION PROPERTIES OF CIRCULATING LYMPHOCYTES
MODIFICATION OF THE MURINE IMMUNE-SYSTEM BY GLUCOCORTICOSTEROIDS - ALTERATIONS OF THE TISSUE LOCALIZATION PROPERTIES OF CIRCULATING LYMPHOCYTES
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DOI：
10.1016/0008-8749(86)90167-x
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发表时间：
1986-09-01
影响因子：
4.3
通讯作者：
DAYNES, RA
中科院分区：
文献类型：
--
作者：
CHUNG, HT;SAMLOWSKI, WE;DAYNES, RA
糖皮质激素已被证明能够通过尚未完全了解的机制来抑制正在发展和正在进行的免疫反应。大多数关于糖皮质激素介导的免疫抑制机制的研究都考察了这些药物对淋巴细胞本身的直接影响。本文分析了糖皮质激素对小鼠淋巴和骨髓淋巴细胞接受能力的影响。这些效应似乎是通过类固醇处理的血管内皮细胞与正常淋巴细胞相互作用能力的可逆变化来介导的，并且具有剂量和时间依赖性。对淋巴细胞定位最显著的影响是通过持续释放的小丸在6天内给予微克量的糖皮质激素的小鼠。淋巴细胞在体外直接暴露于这些药物，对它们随后在体内的定位潜力没有影响。进一步的研究表明，在用糖皮质激素处理的小鼠中，抗原致敏的效应淋巴细胞定位于抗原沉积部位的能力也明显降低。因此，类固醇似乎也对组织相关内皮细胞有影响，从而阻止致敏效应淋巴细胞定位于活跃的炎症部位。我们的观察具有潜在的临床意义，既可以更全面地了解糖皮质类固醇的抗炎作用，也可以提示小剂量持续释放类固醇的应用可能导致免疫抑制增强。
Glucocorticosteroids have proven capable of suppressing both developing and ongoing immune responses via mechanisms that are not fully understood. Most investigations into the mechanisms of glucocorticosteroid-mediated immunosuppression have examined the direct effects of these agents on the lymphocyte itself. In this paper, we have analyzed the effects of glucocorticosteroids on the lymphocyte receptive capacity of lymph nodes and bone marrow in mice. These effects appear to be mediated via reversible changes in the capacity of steroid-treated vascular endothelial cells to interact with normal lymphocytes, and are both dose and time dependent. The most striking effects on lymphocyte localization were observed in mice given microgram quantities of glucocorticosteroids over a 6-day period via a continual release pellet. The direct exposure of lymphocytes to these drugs in vitro was shown to have no effect on their subsequent localization potential in vivo. Further studies revealed that the ability of antigen-sensitized effector lymphocytes to localize into sites of antigen deposition was also markedly depressed in mice pretreated with glucocorticosteroids. Therefore, steroids also appear to have effects on tissue associated endothelial cells which prevent the localization of sensitized effector lymphocytes into sites of active inflammation. Our observations have potential clinical implications, both in understanding the anti-inflammatory effects of glucocorticosteroids more fully, as well as suggesting that low-dose continual-release steroid administration may result in enhanced immunosuppression.