Fiedler Sarah E, George Joshua D, Love Haley N, Kim Edward, Spain Rebecca, Bourdette Dennis, Salinthone Sonemany
VA Portland Health Care System, Research and Development Service, 3710 SW US Veterans' Hospital Rd. Portland, OR 97239, USA.
Department of Neurology, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
J Syst Integr Neurosci. 2017 May;3(3). doi: 10.15761/JSIN.1000166. Epub 2017 Jun 17.
The etiology of multiple sclerosis (MS) is unknown, but blood derived monocytes/macrophages are believed to be involved in the pathogenesis through phagocytosis of myelin and production of inflammatory mediators. The objective of this study is to examine inflammatory cytokines that are present at elevated levels in active MS lesions to determine whether there are differences between classically stimulated monocytes isolated from healthy control (HC) and relapsing-remitting MS (RRMS) subjects taking disease modifying drugs (DMDs), including dimethyl fumarate (DMF).
Thirty-nine veterans of the US Armed Forces were enrolled, 21 health controls (HC), and 18 with relapsing-remitting MS (RRMS), all taking DMDs.
Use ELISAs to measure production of IL-6, IL-1β and TNF-α by LPS-stimulated peripheral monocytes.
Activation of monocytes from MS subjects produced significantly more IL-6 than healthy controls (49531 ± 20795 vs 10526 ± 4845), and IL-6 production trended higher in MS subjects taking DMF than those taking other DMDs (72186.9 ± 35156.2 vs 32585.8 ± 17135.4). There were no significant differences in IL-1β or TNF-α secretion.
Our data suggest that not all DMDs may provide disease modification by suppressing monocyte/macrophage production of pro-inflammatory mediators.
多发性硬化症(MS)的病因尚不清楚,但血液来源的单核细胞/巨噬细胞被认为通过吞噬髓鞘和产生炎症介质参与发病机制。本研究的目的是检测在活动性MS病变中水平升高的炎性细胞因子,以确定从健康对照(HC)和正在服用疾病修饰药物(DMDs)(包括富马酸二甲酯(DMF))的复发缓解型MS(RRMS)受试者中分离出的经典刺激单核细胞之间是否存在差异。
招募了39名美国武装部队退伍军人,其中21名健康对照(HC),18名复发缓解型MS(RRMS)患者,均服用DMDs。
使用酶联免疫吸附测定法(ELISAs)测量脂多糖刺激的外周单核细胞产生白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的情况。
MS受试者的单核细胞活化产生的IL-6明显多于健康对照(49531±20795对10526±4845),并且服用DMF的MS受试者的IL-6产生量比服用其他DMDs的受试者更高(72186.9±35156.2对32585.8±17135.4)。IL-1β或TNF-α分泌没有显著差异。
我们的数据表明,并非所有DMDs都可能通过抑制单核细胞/巨噬细胞产生促炎介质来提供疾病修饰作用。