Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
Neuropathology. 2009 Aug;29(4):433-42. doi: 10.1111/j.1440-1789.2008.00996.x. Epub 2009 Jan 9.
As the pathogenesis of AIDS dementia complex (ADC), cytokines such as TNF-alpha and IL-1beta have been thought to have toxic effects on CNS cells and induce neuronal cell death. However, many of the discussions have been based on the studies done by in vitro experiments. There are only a few reports which demonstrate proinflammatory cytokines directly in vivo in HIV encephalitis (HIVE) brains, and roles of these cytokines with relation to HIV-1 infection are not yet clarified. In the present study, we examined 11 autopsy cases of HIVE using immunohistochemistry, and explored which cell types expressed these cytokines and whether expression of cytokines was related to viral infection. IL-1beta was detected in the frontal white matter of all 11 cases where microglial nodules were observed to varying degrees, whereas TNF-alpha was detected in seven cases. IL-1beta- or TNF-alpha-positive cells were almost restricted to CD68-positive macrophages/microglia and mild expression of these cytokines by astrocytes was observed in two cases with severe HIVE. IL-1beta was detected in some HIVp24-positive multinucleated giant cells. However, we could not detect TNF-alpha expression in the HIVp24-positive cells, which indicates that IL-1beta is induced by HIV-1 infection. In conclusion, a macrophage/microglia lineage is the main cell type to release cytokines in HIVE, and IL-1beta expression by HIV-1-infected cells may be one of the important factors for induction of HIVE. In addition, many non-infected macrophages/microglia as well as some astrocytes express IL-1beta and TNF-alpha, which might contribute to pathogenesis of ADC.
作为艾滋病痴呆综合征（AIDS dementia complex，ADC）的发病机制，细胞因子如 TNF-α 和 IL-1β 被认为对中枢神经系统细胞具有毒性作用，并诱导神经元细胞死亡。然而，许多讨论都是基于体外实验的研究。只有少数报告证明 HIV 脑炎（HIVencephalitis，HIVE）大脑中存在促炎细胞因子，并且这些细胞因子与 HIV-1 感染的关系尚不清楚。在本研究中，我们使用免疫组织化学方法检查了 11 例 HIVE 的尸检病例，探讨了哪些细胞类型表达这些细胞因子，以及细胞因子的表达是否与病毒感染有关。在所有 11 例观察到不同程度小胶质细胞结节的病例中，均检测到 IL-1β 在额叶白质中的表达，而 TNF-α 则在 7 例中检测到。IL-1β 或 TNF-α 阳性细胞几乎局限于 CD68 阳性巨噬细胞/小胶质细胞，并且在 2 例 HIVE 严重的病例中观察到这些细胞因子的轻度表达。在一些 HIVp24 阳性多核巨细胞中检测到 IL-1β。然而，我们无法在 HIVp24 阳性细胞中检测到 TNF-α 的表达，这表明 IL-1β 是由 HIV-1 感染诱导的。总之，巨噬细胞/小胶质细胞谱系是 HIVE 中释放细胞因子的主要细胞类型，HIV-1 感染细胞中 IL-1β 的表达可能是诱导 HIVE 的重要因素之一。此外，许多未感染的巨噬细胞/小胶质细胞以及一些星形胶质细胞表达 IL-1β 和 TNF-α，这可能有助于 ADC 的发病机制。
