Rodriguez M, Pavelko K D, McKinney C W, Leibowitz J L
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
J Immunol. 1994 Oct 15;153(8):3811-21.
We used a murine model of multiple sclerosis (MS) induced by Theiler's murine encephalomyelitis virus (TMEV) to test the effect of IL-6 on central nervous system (CNS) demyelination. Administration of human rIL-6 (2.5 micrograms/dose), beginning one day before infection and then twice daily for 28 days, dramatically reduced demyelination and inflammation in the spinal cord of susceptible SJL/J mice. Benefit also was observed when rIL-6 was used as a therapeutic agent and begun on day 15 after infection, a time in which there is the first evidence of inflammation and demyelination in the spinal cord. Suppression of myelin damage by treatment with rIL-6 was associated with fewer virus Ag-positive cells in the spinal cord. Infectious CNS virus titers, as measured by plaque assay, were reduced in rIL-6-treated animals on day 15 after infection, but not on day 7, 22, or 29 after infection. Total serum Igs and virus-specific Igs, as detected by indirect ELISA, were increased markedly in rIL-6-treated mice, whereas no effect was observed on TMEV-neutralizing Ab titers. In vivo administration of rIL-6 inhibited a murine CNS-demyelinating disease induced by a virus, suggesting that this IL may have application for the treatment of human MS.
我们使用由泰勒氏鼠脑脊髓炎病毒(TMEV)诱导的小鼠多发性硬化症(MS)模型来测试白细胞介素-6(IL-6)对中枢神经系统(CNS)脱髓鞘的影响。从感染前一天开始,每天两次给予人重组IL-6(2.5微克/剂量),持续28天,这显著减轻了易感SJL/J小鼠脊髓中的脱髓鞘和炎症。当将重组IL-6用作治疗剂并在感染后第15天开始使用时也观察到了益处,此时脊髓中首次出现炎症和脱髓鞘的迹象。用重组IL-6治疗对髓鞘损伤的抑制与脊髓中病毒抗原阳性细胞数量减少有关。通过噬斑测定法测量,在感染后第15天,重组IL-6治疗的动物中感染性中枢神经系统病毒滴度降低,但在感染后第7天、22天或29天未降低。通过间接酶联免疫吸附测定法检测,重组IL-6治疗的小鼠中总血清免疫球蛋白和病毒特异性免疫球蛋白显著增加,而对TMEV中和抗体滴度未观察到影响。重组IL-6的体内给药抑制了由病毒诱导的小鼠中枢神经系统脱髓鞘疾病,表明这种白细胞介素可能对治疗人类多发性硬化症有应用价值。