Pullen L C, Miller S D, Dal Canto M C, Van der Meide P H, Kim B S
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611.
J Neuroimmunol. 1994 Dec;55(2):143-52. doi: 10.1016/0165-5728(94)90004-3.
Intracerebral (i.c.) inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. We examined the role of interferon (IFN)-gamma in this virally induced pathogenesis. Intraperitoneal (i.p.) injection of susceptible mice with an IFN-gamma-neutralizing monoclonal antibody (mAb), DB-1, resulted in a significantly accelerated onset of disease. The anti-IFN-gamma mAb-treated animals showed a strong delayed-type hypersensitivity (DTH) response to the virus similar to that of control mAb-treated animals. Treatment with anti-IFN-gamma mAb had no significant effect on the clinical course of disease. However, intracerebral administration of recombinant IFN-gamma significantly accelerated the onset of TMEV-induced disease, as well as enhanced TMEV-specific T cell proliferation and DTH responses. The enhancing effect of IFN-gamma was completely abrogated by simultaneous treatment with anti-IFN-gamma mAb. Collectively, our data suggest that the level of IFN-gamma plays a key role in the TMEV-induced inflammatory response and a perturbation of this balance may result in an alteration in the course of the demyelinating disease.
用泰勒氏鼠脑脊髓炎病毒（TMEV）对易感品系小鼠进行脑内（i.c.）接种会导致免疫介导的脱髓鞘。我们研究了干扰素（IFN）-γ在这种病毒诱导的发病机制中的作用。对易感小鼠腹腔内（i.p.）注射一种IFN-γ中和单克隆抗体（mAb）DB-1，导致疾病发病显著加速。经抗IFN-γ mAb处理的动物对该病毒表现出强烈的迟发型超敏反应（DTH），与经对照mAb处理的动物相似。用抗IFN-γ mAb治疗对疾病的临床进程没有显著影响。然而，脑内给予重组IFN-γ显著加速了TMEV诱导疾病的发病，同时增强了TMEV特异性T细胞增殖和DTH反应。IFN-γ的增强作用通过同时用抗IFN-γ mAb治疗而完全消除。总体而言，我们的数据表明IFN-γ水平在TMEV诱导的炎症反应中起关键作用，这种平衡的扰动可能导致脱髓鞘疾病进程的改变。
