Murine Immunodeficiency Virus-Induced Peripheral Neuropathy and the Associated Cytokine Responses
Murine Immunodeficiency Virus-Induced Peripheral Neuropathy and the Associated Cytokine Responses
复制标题
DOI：
10.4049/jimmunol.1201313
复制
发表时间：
2012-10-01
影响因子：
4.4
通讯作者：
Koh, Woon Yuen
中科院分区：
文献类型：
--
作者：
Cao, Ling;Butler, M. Brady;Koh, Woon Yuen
远端对称性多发性神经病是最常见的HIV感染相关性周围神经病，通常伴有疼痛。感染了LP-BM 5（一种鼠逆转录病毒分离株）的C57 BL/6（B6）小鼠会发展出与感染HIV-1的人类相似的严重免疫缺陷综合征，因此称为鼠AIDS。我们研究了B6小鼠中LP-BM 5感染后周围神经病变的诱导。感染的B6小鼠，像HIV感染的人类，表现出周围神经病变的行为（增加对机械和热刺激的敏感性）和病理（表皮内神经纤维的短暂损失）的迹象。感染后（p.i.），病毒gag RNA的水平在所有测试组织中显著增加，包括脾脏、爪皮肤、腰背根神经节和腰脊髓。与周围神经病变的发展相关，包括IFN-γ、IL-1 β、IL-6和IL-12在内的几种细胞因子的组织水平在p.i.这些增加具有精氨酸特异性和组织特异性特征和动力学。此外，用抗逆转录病毒剂齐多夫定治疗显著减少或完全逆转上述行为、病理和细胞因子变化p.i.这些数据表明，LP-BM 5感染是一种潜在的HIV相关远端对称性多发性神经病小鼠模型，可用于研究各种细胞因子在感染诱导的神经性疼痛中的作用。对该模型的进一步研究可以更好地理解HIV感染相关的疼痛性周围神经病变，并导致更有效的治疗。免疫学杂志，2012，189：3724-3733。
Distal symmetrical polyneuropathy is the most common form of HIV infection-associated peripheral neuropathy and is often associated with pain. C57BL/6 (B6) mice infected with LP-BM5, a murine retroviral isolate, develop a severe immunodeficiency syndrome similar to that in humans infected with HIV-1, hence the term murine AIDS. We investigated the induction of peripheral neuropathy after LP-BM5 infection in B6 mice. Infected B6 mice, like HIV-infected humans, exhibited behavioral (increased sensitivity to mechanical and heat stimuli) and pathological (transient loss of intraepidermal nerve fibers) signs of peripheral neuropathy. The levels of viral gag RNA were significantly increased in all tissues tested, including spleen, paw skin, lumbar dorsal root ganglia, and lumbar spinal cord, postinfection (p.i.). Correlated with the development of peripheral neuropathy, the tissue levels of several cytokines, including IFN-gamma, IL-1 beta, IL-6, and IL-12, were significantly elevated p.i. These increases had cytokine-specific and tissue-specific profiles and kinetics. Further, treatment with the antiretroviral agent zidovudine either significantly reduced or completely reversed the aforementioned behavioral, pathologic, and cytokine changes p.i. These data suggest that LP-BM5 infection is a potential mouse model of HIV-associated distal symmetrical polyneuropathy that can be used for investigating the roles of various cytokines in infection-induced neuropathic pain. Further investigation of this model could give a better understanding of, and lead to more effective treatments for, HIV infection-associated painful peripheral neuropathy. The Journal of Immunology, 2012, 189: 3724-3733.