Stanislaus Romesh, Gilg Anne G, Singh Avtar K, Singh Inderjit
Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
J Autoimmune Dis. 2005 May 3;2(1):4. doi: 10.1186/1740-2557-2-4.
We report that N-acetyl-L-cysteine (NAC) treatment blocked induction of TNF-alpha, IL-1beta, IFN-gamma and iNOS in the CNS and attenuated clinical disease in the myelin basic protein induced model of experimental allergic encephalomyelitis (EAE) in Lewis rats. Infiltration of mononuclear cells into the CNS and induction of inflammatory cytokines and iNOS in multiple sclerosis (MS) and EAE have been implicated in subsequent disease progression and pathogenesis. To understand the mechanism of efficacy of NAC against EAE, we examined its effect on the production of cytokines and the infiltration of inflammatory cells into the CNS. NAC treatment attenuated the transmigration of mononuclear cells thereby lessening the neuroinflammatory disease. Splenocytes from NAC-treated EAE animals showed reduced IFN-gamma production, a Th1 cytokine and increased IL-10 production, an anti-inflammatory cytokine. Further, splenocytes from NAC-treated EAE animals also showed decreased nitrite production when stimulated in vitro by LPS. These observations indicate that NAC treatment may be of therapeutic value in MS against the inflammatory disease process associated with the infiltration of activated mononuclear cells into the CNS.
我们报告，N-乙酰-L-半胱氨酸（NAC）治疗可阻断中枢神经系统（CNS）中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）和诱导型一氧化氮合酶（iNOS）的诱导，并减轻Lewis大鼠髓鞘碱性蛋白诱导的实验性自身免疫性脑脊髓炎（EAE）模型中的临床疾病。单核细胞浸润到中枢神经系统以及在多发性硬化症（MS）和EAE中炎症细胞因子和iNOS的诱导与随后的疾病进展和发病机制有关。为了了解NAC对EAE的疗效机制，我们研究了其对细胞因子产生和炎症细胞浸润到中枢神经系统的影响。NAC治疗减弱了单核细胞的迁移，从而减轻了神经炎症性疾病。来自NAC治疗的EAE动物的脾细胞显示IFN-γ产生减少，IFN-γ是一种Th1细胞因子，而抗炎细胞因子白细胞介素-10的产生增加。此外，来自NAC治疗的EAE动物的脾细胞在体外受到脂多糖刺激时，亚硝酸盐产生也减少。这些观察结果表明，NAC治疗在MS中对于与活化单核细胞浸润到中枢神经系统相关的炎症疾病过程可能具有治疗价值。
