精液和血液中不同的细胞因子/趋化因子网络表征了HIV感染的不同阶段。
Distinct cytokine/chemokine network in semen and blood characterize different stages of HIV infection.
作者信息
Vanpouille Christophe, Introini Andrea, Morris Sheldon R, Margolis Leonid, Daar Eric S, Dube Michael P, Little Susan J, Smith David M, Lisco Andrea, Gianella Sara
机构信息
aNational Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland bUniversity of California-San Diego, La Jolla cLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance dUniversity of Southern California Keck School of Medicine, Los Angeles eVeterans Affairs San Diego Healthcare System, California fNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. *Christophe Vanpouillea and Andrea Introini contributed equally to the writing of this article. †Andrea Introini is currently at the Department of Medicine, Karolinska Institute Hospital, Solna, Stockholm, Sweden. ‡Andrea Lisco and Sara Gianella contributed equally to the writing of this article.
出版信息
AIDS. 2016 Jan;30(2):193-201. doi: 10.1097/QAD.0000000000000964.
OBJECTIVE
The cytokine/chemokine network is used by the innate and adaptive immune system to orchestrate effective immune responses. Here, we describe the cross-sectional association between cytokine levels and stage of HIV infection to gain novel insights into HIV-1 immunopathogenesis and identify novel therapeutic targets.
DESIGN
Concentrations of 31 cytokine/chemokines were retrospectively measured in blood and seminal plasma collected from 252 individuals enrolled in four well characterized cohorts: HIV-uninfected, untreated HIV-infected in early phase of infection, untreated HIV-infected in late phase of infection, and HIV-infected on antiretroviral therapy with undetectable HIV RNA levels in blood (<50 copies/ml).
METHODS
Cytokine/chemokine levels were measured by multiplex-bead array. Comparisons between groups were performed by Mann-Whitney U-test and P values were adjusted for multiple comparisons using the Benjamini-Hochberg method.
RESULTS
Presence of HIV-infection skewed the cytokine/chemokine network towards a pro-inflammatory response in both blood and semen compared to HIV-uninfected controls. Such changes emerged within the first weeks of infection and were maintained thereafter: Among untreated HIV-infected individuals, none of the 31 measured cytokines were significantly different between early and later stages of infection. Suppression of plasma HIV RNA with ART did not result in normalization of the levels of pro-inflammatory cytokines in blood. In semen, several pro-inflammatory cytokines were even further upregulated in ART-treated compared with HIV-uninfected and HIV-untreated individuals.
CONCLUSION
A profound disruption in the cytokine/chemokine network is evident in blood and semen from the earliest stage of HIV infection shortly after the first detection of systemic viremia. These changes are maintained throughout the chronic phase of the infection and do not normalize despite ART and suppression of plasma HIV RNA.
目的
细胞因子/趋化因子网络被先天性和适应性免疫系统用于协调有效的免疫反应。在此，我们描述细胞因子水平与HIV感染阶段之间的横断面关联，以获得对HIV-1免疫发病机制的新见解，并确定新的治疗靶点。
设计
回顾性测量了从252名个体采集的血液和精液中的31种细胞因子/趋化因子浓度，这些个体来自四个特征明确的队列：未感染HIV者、感染早期未接受治疗的HIV感染者、感染晚期未接受治疗的HIV感染者以及接受抗逆转录病毒治疗且血液中HIV RNA水平不可检测（<50拷贝/毫升）的HIV感染者。
方法
通过多重珠阵列测量细胞因子/趋化因子水平。组间比较采用曼-惠特尼U检验，并使用Benjamini-Hochberg方法对P值进行多重比较调整。
结果
与未感染HIV的对照组相比，HIV感染的存在使血液和精液中的细胞因子/趋化因子网络倾向于促炎反应。这种变化在感染后的头几周内出现，并在之后持续存在：在未接受治疗的HIV感染者中，所测量的31种细胞因子在感染早期和晚期之间均无显著差异。抗逆转录病毒疗法抑制血浆HIV RNA并未导致血液中促炎细胞因子水平恢复正常。在精液中，与未感染HIV和未接受治疗的个体相比，接受抗逆转录病毒治疗的个体中几种促炎细胞因子甚至进一步上调。
结论
在首次检测到全身性病毒血症后不久，从HIV感染的最早阶段开始，血液和精液中的细胞因子/趋化因子网络就出现了严重破坏。这些变化在感染的慢性期持续存在，尽管接受了抗逆转录病毒治疗并抑制了血浆HIV RNA，但仍未恢复正常。
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