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来那度胺的免疫调节作用:多发性硬化症可能的新疗法。

Immunomodulation with linomide: possible novel therapy for multiple sclerosis.

作者信息

Abramsky O, Lehmann D, Karussis D

机构信息

Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel.

出版信息

Mult Scler. 1996 Nov;2(4):206-10. doi: 10.1177/135245859600200407.

Abstract

Linomide, a synthetic quinoline carboxamide, has the ability to stimulate various lymphocyte subpopulations. We have shown its inhibitory effect on the clinical and histological signs of acute and chronic relapsing EAE. In these models linomide induces suppression of lymphocyte response to antigens, production of autoantibody, antigen presentation to specific T-cell lines and Mac-I expression, and induces activation of NK and suppressor-inducer cells. We have subsequently shown its inhibitory effect on clinical and MRI signs of patients with secondary progressive multiple sclerosis. Results of a double blind, placebo controlled, short term pilot study with p.o. linomide, showed a significant effect on the clinical disability scale (EDSS) (P = 0.045) and on the mean total number of new lesions in serial monthly MRI scans (P = 0.021). The increase of CD45Ra, CD8 and CD16 positive cells in linomide treated patients may indicate the importance of suppressor-inducer, suppressor and NK cells for the inhibition of the autoimmune response in the disease.

摘要

来那度胺是一种合成喹啉羧酰胺,具有刺激多种淋巴细胞亚群的能力。我们已经证明它对急性和慢性复发性实验性自身免疫性脑脊髓炎(EAE)的临床和组织学表现具有抑制作用。在这些模型中,来那度胺可抑制淋巴细胞对抗原的反应、自身抗体的产生、向特定T细胞系的抗原呈递以及Mac-1表达,并诱导自然杀伤细胞(NK)和抑制诱导细胞的激活。我们随后证明了它对继发进展型多发性硬化症患者的临床和磁共振成像(MRI)表现具有抑制作用。一项口服来那度胺的双盲、安慰剂对照短期初步研究结果显示,其对临床残疾量表(EDSS)有显著影响(P = 0.045),对每月连续MRI扫描中新病灶的平均总数也有显著影响(P = 0.021)。来那度胺治疗患者中CD45Ra、CD8和CD16阳性细胞的增加可能表明抑制诱导细胞、抑制细胞和NK细胞在抑制该疾病自身免疫反应中的重要性。

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