Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA, United States.
Cytokine Growth Factor Rev. 2012 Feb-Apr;23(1-2):7-14. doi: 10.1016/j.cytogfr.2012.01.001. Epub 2012 Feb 17.
Clinical studies indicate that increased central nervous system (CNS) interferon-alpha (IFNα) is associated with cognitive dysfunction in a wide variety of conditions. This has perhaps been best studied in HIV-associated neurocognitive disorders (HAND). These findings on IFNα neurotoxicity have been corroborated in animal studies. Probably the best demonstration of the neurotoxicity of IFNα was through the use of a mouse model of HAND, where it was shown that blocking IFNα with neutralizing antibodies prevented behavioral deficits and associated histopathological effects. In vitro studies have demonstrated a dose dependent, detrimental effect of IFNα on neuronal dendrites. Development of therapeutics that block IFNα may prove to be an effective treatment of HAND and other inflammatory conditions where there is increased CNS IFNα.
临床研究表明，中枢神经系统（CNS）干扰素-α（IFNα）水平升高与多种情况下的认知功能障碍有关。在 HIV 相关神经认知障碍（HAND）中对此研究得最为透彻。这些关于 IFNα 神经毒性的发现已在动物研究中得到证实。IFNα 神经毒性的最佳证明可能是通过使用 HAND 的小鼠模型，研究表明，用中和抗体阻断 IFNα 可防止行为缺陷和相关的组织病理学影响。体外研究表明，IFNα 对神经元树突有剂量依赖性的有害影响。开发阻断 IFNα 的疗法可能被证明是治疗 HAND 和其他 CNS IFNα 升高的炎症性疾病的有效方法。
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