Nizri Eran, Irony-Tur-Sinai Michal, Faranesh Nabil, Lavon Iris, Lavi Ehud, Weinstock Marta, Brenner Talma
Laboratory of Neuroimmunology, Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Jerusalem, Israel.
J Neuroimmunol. 2008 Oct 15;203(1):12-22. doi: 10.1016/j.jneuroim.2008.06.018.
In this study we determined the influence of cholinergic up-regulation by rivastigmine, an acetylcholinesterase inhibitor, on central nervous system inflammation. Neuroinflammation was induced in experimental autoimmune encephalomyelitis (EAE). Rivastigmine markedly ameliorated clinical symptoms of EAE and the spatial memory deficits induced by EAE. It also reduced demyelination, microglia activation and axonal damage. Rivastigmine decreased the reactivity of encephalitogenic T-cells and the production of pro-inflammatory cytokines (TNF-alpha, IFN-gamma and IL-17) without affecting IL-10 production. These effects were abolished by alpha7 nicotinic acetylcholine receptor antagonists. Antigen presentation was also affected by this treatment. Thus, rivastigmine treatment had immunomodulatory activity in EAE.
在本研究中,我们确定了乙酰胆碱酯酶抑制剂卡巴拉汀引起的胆碱能上调对中枢神经系统炎症的影响。在实验性自身免疫性脑脊髓炎(EAE)中诱导神经炎症。卡巴拉汀显著改善了EAE的临床症状以及由EAE诱导的空间记忆缺陷。它还减少了脱髓鞘、小胶质细胞活化和轴突损伤。卡巴拉汀降低了致脑炎性T细胞的反应性以及促炎细胞因子(肿瘤坏死因子-α、干扰素-γ和白细胞介素-17)的产生,而不影响白细胞介素-10的产生。α7烟碱型乙酰胆碱受体拮抗剂消除了这些作用。这种治疗也影响了抗原呈递。因此,卡巴拉汀治疗在EAE中具有免疫调节活性。