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锌络氨酸与静脉注射免疫球蛋白联合治疗可改善实验性自身免疫性脑脊髓炎(EAE)。

Combined Treatment with Zinc Aspartate and Intravenous Immunoglobulins (IVIGs) Ameliorates Experimental Autoimmune Encephalomyelitis (EAE).

机构信息

Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

University Clinic of Dermatology and Venereology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

出版信息

J Immunol Res. 2018 Sep 26;2018:5982169. doi: 10.1155/2018/5982169. eCollection 2018.

Abstract

Intravenous immunoglobulins (IVIGs) are widely used in replacement therapy of primary and secondary immunodeficiency disorders and in approved autoimmune indications. In addition, IVIG application is used off-label for treatment of other autoimmune diseases, e.g., multiple sclerosis (MS), an inflammatory autoimmune disorder with a clear T cell-mediated immune pathogenesis. The trace element zinc is shown to play a regulatory role in the maintenance of immune functions. Changes of zinc homeostasis affect both the innate and the adaptive immune system. On one hand, therapeutic zinc supplementation can normalize impaired immune functions due to zinc deficiency. On the other hand, therapeutic zinc supplementation is under consideration as a possible option to treat T cell-mediated autoimmune diseases. The aim of the present study was to investigate the influence of IVIG (Octagam®), zinc aspartate (Unizink®), and the combined application of both preparations in the experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Therapeutic intraperitoneal application of zinc aspartate significantly diminished clinical signs during the relapsing-remitting phase of EAE in SJL/J mice. In contrast, IVIG given in a therapeutic manner did not influence the course of EAE. Interestingly, the combined application of both, IVIG and zinc aspartate, significantly reduced the severity of the disease during the acute and the relapsing-remitting phase of the EAE. Our data suggest that the combination of IVIG and zinc aspartate may have beneficial effects in autoimmune diseases, like MS. Further studies should verify the benefit of a controlled immunosuppressive therapy with IVIG and zinc for such diseases.

摘要

静脉注射免疫球蛋白(IVIGs)广泛用于原发性和继发性免疫缺陷疾病的替代治疗以及已批准的自身免疫适应症。此外,IVIG 的应用还被超适应证用于治疗其他自身免疫性疾病,例如多发性硬化症(MS),这是一种具有明确 T 细胞介导免疫发病机制的炎症性自身免疫性疾病。微量元素锌被证明在维持免疫功能方面发挥着调节作用。锌平衡的变化会影响固有免疫和适应性免疫系统。一方面,治疗性锌补充可以使因锌缺乏而受损的免疫功能正常化。另一方面,治疗性锌补充被认为是治疗 T 细胞介导的自身免疫性疾病的一种可能选择。本研究的目的是研究 IVIG(Octagam®)、锌天冬氨酸(Unizink®)和两者联合应用对实验性自身免疫性脑脊髓炎(EAE),即 MS 的动物模型的影响。在 SJL/J 小鼠的复发缓解期,腹腔内给予治疗性锌天冬氨酸可显著减轻 EAE 的临床症状。相比之下,以治疗方式给予 IVIG 并不影响 EAE 的病程。有趣的是,IVIG 和锌天冬氨酸联合应用可显著减轻 EAE 的急性期和复发缓解期的疾病严重程度。我们的数据表明,IVIG 和锌天冬氨酸的联合应用可能对 MS 等自身免疫性疾病有益。进一步的研究应验证 IVIG 和锌的控制性免疫抑制治疗对这些疾病的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc1/6178489/85cc89a898c5/JIR2018-5982169.001.jpg

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