Kadhim Hazim, De Prez Carine, Gazagnes Marie-Dominique, Sébire Guillaume
Unité de Neuropathologie, Service d'Anatomopathologie, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
Hum Pathol. 2003 Mar;34(3):293-7. doi: 10.1053/hupa.2003.34.
Acute disseminated encephalomyelitis (ADEM) is thought to be an autoimmune disorder of the central nervous system in which myelin is targeted. Pathological studies on closely related human diseases (eg, multiple sclerosis) and on animal models for these demyelinating disorders have suggested the involvement of cytokines. Studies on peripheral immunocytes and on cerebrospinal fluid revealed the presence of cytokine-mediated responses in ADEM. We carried out this neuroimmunopathologic exploration and report for the first time the in situ expression of "inflammatory" cytokines in ADEM. Moreover, we note a particular spatial and molecular pattern whereby tumor necrosis factor-alpha and interleukin (IL)-1beta are intensely expressed, whereas IL-6 is absent. Differential expression at different levels of the neuraxis was also noticed. Our findings suggest that these cytokines, reported to be toxic to myelin, are implicated in the molecular cascade, resulting in the neural damage. These observations might provide insights into molecular pathways involved in the immunopathogenesis of ADEM and might open new horizons in neuroimmunomodulation and anticytokine treatment.
急性播散性脑脊髓炎（ADEM）被认为是一种以髓鞘为靶点的中枢神经系统自身免疫性疾病。对密切相关的人类疾病（如多发性硬化症）以及这些脱髓鞘疾病动物模型的病理学研究表明细胞因子参与其中。对外周免疫细胞和脑脊液的研究揭示了ADEM中存在细胞因子介导的反应。我们进行了这项神经免疫病理学探索，并首次报告了ADEM中“炎症性”细胞因子的原位表达。此外，我们注意到一种特殊的空间和分子模式，即肿瘤坏死因子-α和白细胞介素（IL）-1β强烈表达，而IL-6缺失。在神经轴不同水平的差异表达也被注意到。我们的研究结果表明，这些据报道对髓鞘有毒性的细胞因子参与了分子级联反应，导致神经损伤。这些观察结果可能为ADEM免疫发病机制所涉及的分子途径提供见解，并可能为神经免疫调节和抗细胞因子治疗开辟新的前景。
