Kasarełło K, Szczepankowska A, Kwiatkowska-Patzer B, Lipkowski A W, Gadamski R, Sulejczak D, Łachwa M, Biały M, Bardowski J
Kaja Kasarełło, Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha St, 02-097 Warsaw, Poland, phone: +48 22 116 6113, e-mail:
Folia Neuropathol. 2016;54(3):249-258. doi: 10.5114/fn.2016.62534.
Multiple sclerosis (MS) is a human autoimmune neurodegenerative disease with an unknown etiology. Despite various therapies, there is no effective cure for MS. Since the mechanism of the disease is based on autoreactive T-cell responses directed against myelin antigens, oral tolerance is a promising approach for the MS treatment. Here, the experiments were performed to assess the impact of oral administration of recombinant Lactococcus lactis producing encephalogenic fragments of three myelin proteins: myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein, on neuroimmunological changes in rats with experimental allergic encephalomyelitis (EAE) - an animal model of MS. Lactococcus lactis whole-cell lysates were administered intragastrically at two doses (103 and 106 colony forming units) in a twenty-fold feeding regimen to Lewis rats with EAE. Spinal cord slices were subjected to histopathological analysis and morphometric evaluation, and serum levels of cytokines (IL-1b, IL-10, TNF-α and IFN-γ) were measured. Results showed that administration of the L. lactis preparations at the tested doses to rats with EAE, diminished the histopathological changes observed in EAE rats and reduced the levels of serum IL-1b, IL-10 and TNF-α, previously increased by evoking EAE. This suggests that oral delivery of L. lactis producing myelin peptide fragments could be an alternative strategy to induce oral tolerance for the treatment of MS.
多发性硬化症（MS）是一种病因不明的人类自身免疫性神经退行性疾病。尽管有多种治疗方法，但MS尚无有效治愈方法。由于该疾病的机制基于针对髓鞘抗原的自身反应性T细胞反应，口服耐受是一种有前景的MS治疗方法。在此，进行实验以评估口服表达三种髓鞘蛋白（髓鞘碱性蛋白、蛋白脂蛋白和髓鞘少突胶质细胞糖蛋白）脑源性片段的重组乳酸乳球菌对实验性自身免疫性脑脊髓炎（EAE，MS的动物模型）大鼠神经免疫学变化的影响。将乳酸乳球菌全细胞裂解物以两种剂量（10³和10⁶菌落形成单位）通过二十倍喂食方案灌胃给予患有EAE的Lewis大鼠。对脊髓切片进行组织病理学分析和形态计量学评估，并测量细胞因子（IL-1β、IL-10、TNF-α和IFN-γ）的血清水平。结果表明，将测试剂量的乳酸乳球菌制剂给予患有EAE的大鼠，可减轻EAE大鼠中观察到的组织病理学变化，并降低血清IL-1β、IL-10和TNF-α的水平，这些细胞因子在诱发EAE后先前有所升高。这表明口服表达髓鞘肽片段的乳酸乳球菌可能是诱导口服耐受以治疗MS的替代策略。
