Cinque Paola, Bestetti Arabella, Marenzi Roberta, Sala Serena, Gisslen Magnus, Hagberg Lars, Price Richard W
Clinic of Infectious Diseases, San Raffaele Hospital, Milan, Italy.
J Neuroimmunol. 2005 Nov;168(1-2):154-63. doi: 10.1016/j.jneuroim.2005.07.002. Epub 2005 Aug 8.
Interferon-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant and has been suggested to enhance retrovirus infection and mediate neuronal injury. In order to assess this chemokine in central nervous system (CNS) HIV infection, we measured the cerebrospinal fluid (CSF) and plasma concentrations of CXCL10 by immunoassay in samples derived from 97 HIV-infected subjects across a spectrum of immunological progression and CNS complications and from 16 HIV seronegative control subjects studied at three clinical centers between 1994 and 2001. We also examined changes in the CSF and plasma CXCL10 concentrations in 30 subjects starting and three stopping antiretroviral therapy. CSF CXCL10 concentrations: (1) correlated with CSF HIV RNA and white blood cell (WBC) counts, but not with blood CXCL10, HIV RNA, or CD4 counts; (2) were increased in subjects with primary and asymptomatic HIV infections and AIDS dementia complex, but less frequently in those with more advanced infection, with or without CNS opportunistic diseases except cytomegalovirus encephalitis; (3) decreased in subjects starting antiretroviral in association with decreases in CSF and plasma HIV RNA and CSF WBCs; and (4) conversely, increased in subjects stopping treatment in parallel with CSF HIV RNA and WBCs. These results confirm that CSF CXCL10 associates closely with both CSF HIV and WBCs and suggest that this chemokine may be both a response to and contributing determinant of local infection. High CSF levels may be useful in the diagnosis of ADC in subjects with advanced immunosuppression in whom CMV encephalitis has been ruled out, though this issue requires further study.
γ-干扰素诱导蛋白（IP-10或CXCL10）是一种有效的趋化因子，有人认为它可增强逆转录病毒感染并介导神经元损伤。为了评估这种趋化因子在中枢神经系统（CNS）HIV感染中的作用，我们采用免疫分析法测定了1994年至2001年间在三个临床中心研究的97例处于不同免疫进展阶段和CNS并发症阶段的HIV感染受试者以及16例HIV血清阴性对照受试者的脑脊液（CSF）和血浆中CXCL10的浓度。我们还检测了30例开始抗逆转录病毒治疗和30例停止抗逆转录病毒治疗的受试者CSF和血浆中CXCL10浓度的变化。CSF CXCL10浓度：（1）与CSF HIV RNA和白细胞（WBC）计数相关，但与血液CXCL10、HIV RNA或CD4计数无关；（2）在原发性和无症状HIV感染及艾滋病痴呆综合征患者中升高，但在感染更严重的患者中升高频率较低，无论有无CNS机会性疾病（巨细胞病毒性脑炎除外）；（3）在开始抗逆转录病毒治疗的受试者中降低，同时CSF和血浆HIV RNA及CSF WBC减少；（4）相反，在停止治疗的受试者中升高，与CSF HIV RNA和WBC平行升高。这些结果证实CSF CXCL10与CSF HIV和WBC密切相关，并表明这种趋化因子可能既是局部感染的反应因素，也是其决定因素。在已排除巨细胞病毒性脑炎的晚期免疫抑制患者中，高CSF水平可能有助于诊断艾滋病痴呆综合征，不过这个问题还需要进一步研究。
