Cinque P, Vago L, Mengozzi M, Torri V, Ceresa D, Vicenzi E, Transidico P, Vagani A, Sozzani S, Mantovani A, Lazzarin A, Poli G
Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
AIDS. 1998 Jul 30;12(11):1327-32. doi: 10.1097/00002030-199811000-00014.
To investigate whether the CC-chemokine monocyte chemotactic protein (MCP)-1 could play a role in the pathogenesis of HIV infection of the central nervous system. This hypothesis was suggested by previous observations, including our finding of elevated cerebrospinal fluid (CSF) levels of this chemokine in patients with cytomegalovirus (CMV) encephalitis.
CSF levels of MCP-1 were determined in 37 HIV-infected patients with neurological symptoms, and were compared with both the presence and severity of HIV-1 encephalitis at post-mortem examination and CSF HIV RNA levels. MCP-1 production by monocyte-derived macrophages was tested after in vitro infection of these cells by HIV.
CSF MCP-1 levels were significantly higher in patients with (median, 4.99 ng/ml) than in those without (median, 1.72 ng/ml) HIV encephalitis. Elevated CSF MCP-1 concentrations were also found in patients with CMV encephalitis and with concomitant HIV and CMV encephalitis (median, 3.14 and 4.23 ng/ml, respectively). HIV encephalitis was strongly associated with high CSF MCP-1 levels (P = 0.002), which were also correlated to high HIV-1 RNA levels in the CSF (P = 0.007), but not to plasma viraemia. In vitro, productive HIV-1 infection of monocyte-derived macrophages upregulated the secretion of MCP-1.
Taken together, these in vivo and in vitro findings support a model whereby HIV encephalitis is sustained by virus replication in microglial cells, a process amplified by recruitment of mononuclear cells via HIV-induced MCP-1.
研究CC趋化因子单核细胞趋化蛋白（MCP）-1是否在人类免疫缺陷病毒（HIV）感染中枢神经系统的发病机制中发挥作用。先前的观察结果提示了这一假设，包括我们发现巨细胞病毒（CMV）脑炎患者脑脊液（CSF）中该趋化因子水平升高。
测定了37例有神经症状的HIV感染患者的CSF中MCP-1水平，并将其与尸检时HIV-1脑炎的存在情况和严重程度以及CSF中HIV RNA水平进行比较。在这些细胞被HIV体外感染后，检测单核细胞衍生巨噬细胞产生MCP-1的情况。
有HIV脑炎的患者CSF中MCP-1水平（中位数为4.99 ng/ml）显著高于无HIV脑炎的患者（中位数为1.72 ng/ml）。在CMV脑炎患者以及合并HIV和CMV脑炎的患者中也发现CSF中MCP-1浓度升高（分别为中位数3.14和4.23 ng/ml）。HIV脑炎与高CSF MCP-1水平密切相关（P = 0.002），CSF中MCP-1水平也与CSF中高HIV-1 RNA水平相关（P = 0.007），但与血浆病毒血症无关。在体外，单核细胞衍生巨噬细胞的HIV-1有效感染上调了MCP-1的分泌。
综上所述，这些体内和体外研究结果支持了一种模型，即HIV脑炎由小胶质细胞中的病毒复制维持，这一过程通过HIV诱导的MCP-1募集单核细胞而放大。
