The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro

被引：71

作者：

Li, Li ^{[1
]}

Liu, Jingchun ^{[1
]}

Delohery, Thomas ^{[1
]}

Zhang, Donghui ^{[2
]}

Arendt, Christopher ^{[1
]}

Jones, Catherine ^{[1
]}

机构：

[1] Sanofi, BioInnovat Grp, Cambridge, MA 02139 USA

[2] Sanofi, Global Biostat & Programming, Bridgewater, NJ USA

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2013年 / 265卷 / 1-2期

关键词：

Multiple sclerosis; Immunomodulation; Anti-inflammatory; Anti-proliferative; CNS; De novo pyrimidine synthesis; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; T-CELL; MICE; DISEASE; IL-6; PATHOGENESIS; CCL2; DIFFERENTIATION;

D O I：

10.1016/j.jneuroim.2013.10.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Teriflunomide is an inhibitor of dihydro-orotate dehydrogenase (DHODH), and is hypothesized to ameliorate multiple sclerosis by reducing proliferation of stimulated lymphocytes. We investigated teriflunomide's effects on proliferation, activation, survival, and function of stimulated human peripheral blood mononuclear cell subsets in vitro. Teriflunomide had little/no impact on lymphocyte activation but exerted significant dose-dependent inhibition of T- and B-cell proliferation, which was uridine-reversible (DHODH-dependent). Viability analyses showed no teriflunomide-associated cytotoxicity. Teriflunomide significantly decreased release of several pro-inflammatory cytokines from activated monocytes in a DHODH-independent fashion. In conclusion, teriflunomide acts on multiple immune cell types and processes via DHODH-dependent and independent mechanisms. (C) 2013 Elsevier B.V. All rights reserved.

引用

页码：82 / 90

页数：9

共 41 条

[1] Comparing the pathogenesis of experimental autoimmune encephalomyelitis in CD4-/- and CD8-/- DBA/1 mice defines qualitative roles of different T cell subsets [J].