Methylenedioxymethamphetamine (MDMA; Ecstasy) suppresses IL-1β and TNF-α secretion following an in vivo lipopolysaccharide challenge
Methylenedioxymethamphetamine (MDMA; Ecstasy) suppresses IL-1β and TNF-α secretion following an in vivo lipopolysaccharide challenge
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DOI：
10.1016/s0024-3205(00)00743-8
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发表时间：
2000-08-18
期刊：
影响因子：
6.1
通讯作者：
Leonard, BE
中科院分区：
文献类型：
--
作者：
Connor, TJ;Kelly, JP;Leonard, BE
在这项研究中，我们研究了亚甲基二氧基甲基苯丙胺（MDMA）给药对脂多糖（LPS; 100 μ g/kg; i.p.）体内免疫攻击的反应性的影响。LPS使对照动物的循环IL-1 β和tnf - α增加。MDMA （20 mg/kg; i.p）显著损害lps诱导的IL-1 β和tnf - α分泌。MDMA对IL-1 β分泌的抑制作用是短暂的，并在给药3小时内恢复到控制水平。相反，mdma诱导的tnf - α分泌抑制在给药后12小时内是明显的。在第二项研究中，我们检测了MDMA铜给药（5、10和20 mg/kg； i.p）对lps诱导的IL-1 β和tnf - α分泌的影响，并证明这三种剂量都能有效抑制lps诱导的tnf - α分泌，但只有MDMA 10和20 mg/kg抑制lps诱导的IL-1 β分泌。此外，血清MDMA浓度呈剂量依赖性增加，在给药5和10 mg/kg后达到的浓度在人类MDMA滥用者中报告的范围内。为了检验MDMA对IL-1 β和tnf - α的抑制作用可能是由于药物对免疫细胞的直接作用，我们评估了体外暴露于MDMA对lps刺激的稀释全血中IL-1 β和tnf - α产生的影响。然而，IL-1 β或tnf - α的产生并未因体外暴露于MDMA而改变。总之，这些数据表明，在体内LPS刺激后，急性MDMA给药会损害IL-1 β和tnf - α的分泌，并且tnf - α对MDMA的抑制作用比IL-1 β更敏感。然而，MDMA对IL-1 β和tnf - α的抑制作用不能归因于对免疫细胞的直接作用。这些发现与mdma诱导的免疫调节的相关性进行了讨论。(C) 2000 Elsevier Science Inc.；版权所有。
In this study we examined the effects of methylenedioxymethamphetamine (MDMA) administration on responsiveness to an in vivo immune challenge with lipopolysaccharide (LPS; 100 mu g/kg; i.p.). LPS produced an increase in circulating IL-1 beta and TNF-alpha in control animals. MDMA (20 mg/kg; i.p.) significantly impaired LPS-induced IL-1 beta and TNF-alpha secretion. The suppressive effect of MDMA on IL-1 beta secretion was transient and returned to control levels within 3 hours of administration. In contrast, the MDMA-induced suppression of TNF-alpha secretion was evident for up to 12 hours following administration. In a second study we examined the effect of cu-administration of MDMA (5, 10 and 20 mg/kg; i.p.) on LPS-induced IL-1 beta and TNF-alpha secretion, and demonstrated that all three doses potently suppressed LPS-induced TNF-alpha secretion, but only MDMA 10 and 20 mg/kg suppressed LPS-induced IL-1 beta secretion. In addition, serum MDMA concentrations displayed a dose-dependent increase, with the concentrations achieved following administration of 5 and 10 mg/kg being in the range reported in human MDMA abusers. In order to examine the possibility that the suppressive effect of MDMA on IL-1 beta and TNF-alpha could be due to a direct effect of the drug on immune cells, the effect of in vitro exposure to MDMA on IL-1 beta and TNF-alpha production in LPS-stimulated diluted whole blood was evaluated. However IL-1 beta or TNF-alpha production were not altered by in vitro exposure to MDMA. in conclusion, these data demonstrate that acute MDMA administration impairs IL-1 beta and TNF-alpha secretion following an in vivo LPS challenge, and that TNF-alpha is more sensitive to the suppressive effects of MDMA than is IL-1 beta. However the suppressive effect of MDMA on IL-1 beta and TNF-alpha could not be attributed to a direct effect on immune cells. The relevance of these findings to MDMA-induced immunomodulation is discussed. (C) 2000 Elsevier Science Inc. All rights reserved.