The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study
The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study
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DOI：
10.1177/1352458506070319
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发表时间：
2007-05-01
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影响因子：
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通讯作者：
Yong, V. W.
中科院分区：
文献类型：
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作者：
Zabad, R. K.;Metz, L. M.;Yong, V. W.
米诺环素在体外和多发性硬化症(MS)动物模型中具有免疫调节和神经保护活性。我们此前曾在一项针对活动期复发缓解型多发性硬化症(RRMS)患者的小型试验中报道，米诺环素在六个月内降低了Gd增强活性。在这里，我们报告了口服米诺环素对米诺环素开放治疗24个月的临床和磁共振成像(MRI)结果以及血清免疫分子的影响。尽管治疗前的年化复发率中等偏高(登记前为1.3/年；三个月基线期间为1.2/年)，但在6个月至24个月期间没有复发。此外，尽管MRI活动非常活跃(19/40扫描在三个月的磨合期间有Gd增强活性)，但在12个月和24个月时MRI显示Gd增强病变的唯一患者是服用一半剂量的米诺环素。在18个月的治疗中，IL-12的p40亚单位的水平以及可溶性血管细胞黏附分子-1的水平都有所上升，而IL-12的高水平可能会对抗促炎的IL-12受体。治疗后基质金属蛋白酶-9活性降低。因此，临床和MRI结果得到了系统免疫学变化的支持，并呼吁进一步研究米诺环素在MS中的作用。
Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.