Elevated expression of IFN-gamma in the HIV-1 infected brain
Elevated expression of IFN-gamma in the HIV-1 infected brain
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DOI：
10.2741/1271
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发表时间：
2004-05-01
影响因子：
3.1
通讯作者：
Goodkin, K
中科院分区：
文献类型：
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作者：
Shapshak, P;Duncan, R;Goodkin, K
我们确定了三种细胞因子（IFN-γ，IL-4和TNF-α）在人类免疫缺陷病毒-1（HIV-1）感染的脑组织中的表达程度。选择IFN-γ作为Th 1细胞因子，IL-4作为Th 2细胞因子，TNF-α作为促炎细胞因子（并且因为其先前在由于HIV-1感染引起的脑组织损伤中的含义）。基于目前的HIV-1相关痴呆（HAD）发病机制模型，在外周，Th 1细胞因子被认为是有益的，而Th 2细胞因子被认为是有害的。然而，我们假设在中枢神经系统中，这些作用是颠倒的。采用免疫组织化学和碱性磷酸酶对16例HIV-1血清阳性患者和11例HIV-1血清阴性对照的死后颞叶组织标本进行IFN-γ、IL-4和TNF-α染色。HIV-1感染引起脑细胞因子表达的改变，包括HIV-1血清阳性与HIV-1血清阴性个体的IFN-γ表达增加。与HIV-1血清阴性者相比，HIV-1血清阳性者伴或不伴HAD、伴或不伴更广泛的神经精神损害（NPI）、伴或不伴机会性感染（OIs）的IFN-γ表达增加。观察到HIV-1血清阳性HAD和血清阴性个体中IFN-γ与IL-4之间的显著负相关。IFN-γ与TNF-α之间的血清阳性呈负相关，HAD呈阳性趋势，无HAD时具有显著性，NPI具有显著性，无OI时具有显著性。IL-4与TNF-α之间在血清阳性中存在相关性（趋势），与NPI呈趋势，在无NPI时具有显著性，在无OI时呈趋势。由于脑和神经系统疾病的HIV-1感染，IFN-γ的表达显著增加，IFN-γ相对于TNF-α和TNF-α相对于IL-4的表达相反。IFN-γ增加和IL-4表达减少之间的负相关性与活化的巨噬细胞和T细胞的刺激一致，在HIV-1感染的脑中具有更大的毒性，并且支持IFN-γ在HIV-1感染的患者中的意义。
We determined the extent of expression of three cytokines (IFN-gamma, IL-4, and TNF-alpha) in brain tissue infected with human immunodeficiency virus-1 (HIV-1). The selections were IFN-gamma as a Th1 cytokine, IL-4 as a Th2 cytokine, and TNF-alpha as a pro-inflammatory cytokine ( and because of its prior implication in brain tissue damage due to HIV-1 infection). Based on current models for pathogenesis of HIV-1-associated dementia ( HAD), in the periphery, Th1 cytokines are considered to be salutary, whereas Th2 cytokines are regarded as deleterious. However, we hypothesized that in the CNS these roles are reversed. Post-mortem temporal lobe tissue specimens from 16 HIV-1-seropositive patients and 11 HIV-1-seronegative controls were stained for IFN-gamma, IL-4, and TNF-alpha utilizing immunohistochemistry and alkaline phosphatase. HIV-1 infection causes alterations of brain cytokine expression that include increased IFN-gamma expression for HIV-1-seropositive vs. HIV-1-seronegative individuals. There was increased expression of IFN-gamma for HIV-1-seropositive individuals with or without HAD, with or without the broader category of neuropsychiatric impairment (NPI), and with or without opportunistic infections (OIs) compared to HIV-1-seronegatives. A significant inverse correlation between IFN-gamma vs. IL-4 in HIV-1-seropositives with HAD and in seronegative individuals was observed. There was an inverse correlation in seropositives between IFN-gamma vs. TNF-alpha, a positive trend with HAD, significant without HAD, significant with NPI and significant without OIs. Between IL-4 vs. TNF-alpha there was a correlation ( trend) in seropositives, a trend with NPI, significant without NPI, and a trend without OI. Due to HIV-1 infection of the brain and neurological disease there is a prominent increased expression of IFN-gamma, an inverse expression of IFN-gamma vs. TNF-alpha, and TNF-alpha vs. IL-4. The inverse correlation between increased IFN-gamma and decreased IL-4 expression is consistent with the stimulation of activated macrophages, and T cells, greater toxicity in the HIV-1-infected brain, and is supportive of the significance of IFN-gamma in HIV-1-infected patients.