Gherardi R K, Florea-Strat A, Fromont G, Poron F, Sabourin J C, Authier J
Department of Pathology (Neuropathology), Hôpital Henri Mondor, Créteil, France.
Ann Neurol. 1994 Nov;36(5):752-8. doi: 10.1002/ana.410360511.
To evaluate the possible role of cytokines in human immunodeficiency virus (HIV)-associated muscular disorders, we performed immunocytochemistry for interleukin-1 alpha, -1 beta, and -6 and tumor necrosis factor-alpha on frozen muscle biopsy specimens from HIV-infected patients with various myopathies (HIV polymyositis in 5, HIV-wasting syndrome in 5, zidovudine myopathy in 10) and from seronegative individuals (normal muscle in 2, mitochondrial cytopathies in 10). The HIV-infected patients showed positive reactivities in vessels (interleukin-1) and in inflammatory cells (mainly interleukin-1 and tumor necrosis factor-alpha), including perivascular hemosiderin-laden macrophages in 5 patients. In zidovudine myopathy, a majority of AZT fibers (i.e., ragged-red fibers with marked myofibrillar changes) showed mild to marked expression of interleukin-1. Expression of interleukin-1 in the other mitochondrial myopathies was much weaker. Interleukin-1 beta messenger RNA was demonstrated in muscle fibers by in situ hybridization, implying that interleukin-1 was produced in muscle cells. Immunoelectron microscopy showed that interleukin-1 alpha was mainly bound to mitochondrial membranes in AZT fibers. Proinflammatory and destructive effects of the studied cytokines might be responsible for several myopathological changes observed in HIV-infected patients, including inflammation and hemosiderin deposits in muscle tissue, and prominent myofibrillar breakdown in AZT fibers.
为评估细胞因子在人类免疫缺陷病毒（HIV）相关肌肉疾病中可能发挥的作用，我们对HIV感染的各种肌病患者（5例HIV多发性肌炎、5例HIV消瘦综合征、10例齐多夫定肌病）以及血清反应阴性个体（2例正常肌肉、10例线粒体细胞病）的冷冻肌肉活检标本进行了白细胞介素-1α、-1β、-6和肿瘤坏死因子-α的免疫细胞化学检测。HIV感染患者的血管（白细胞介素-1）和炎症细胞（主要是白细胞介素-1和肿瘤坏死因子-α）呈现阳性反应，5例患者的血管周围可见含铁血黄素巨噬细胞。在齐多夫定肌病中，大多数齐多夫定纤维（即具有明显肌原纤维改变的破碎红纤维）显示白细胞介素-1呈轻度至明显表达。白细胞介素-1在其他线粒体肌病中的表达则弱得多。原位杂交显示肌肉纤维中有白细胞介素-1β信使核糖核酸，这意味着白细胞介素-1是在肌肉细胞中产生的。免疫电子显微镜显示，白细胞介素-1α主要与齐多夫定纤维中的线粒体膜结合。所研究细胞因子的促炎和破坏作用可能是HIV感染患者中观察到的几种肌病病理变化的原因，包括肌肉组织中的炎症和含铁血黄素沉积，以及齐多夫定纤维中明显的肌原纤维破坏。
