French Martyn A, Cozzi-Lepri Alessandro, Arduino Roberto C, Johnson Margaret, Achhra Amit C, Landay Alan
aSchool of Pathology and Laboratory Medicine, University of Western Australia bDepartment of Clinical Immunology, Royal Perth Hospital and PathWest, Laboratory Medicine, Perth, Australia cResearch Department of Infection and Population Health, University College London, London, United Kingdom dHouston AIDS Research Team, Division of Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, USA eHIV Clinic and Department of Respiratory Medicine, Royal Free Hospital, London, United Kingdom fKirby Institute, University of New South Wales, Sydney, Australia gDepartment of Immunology and Microbiology, Rush University Medical Center, Chicago, USA.
AIDS. 2015 Apr 24;29(7):847-51. doi: 10.1097/QAD.0000000000000618.
All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin-6 which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs.
Baseline plasma samples from 142 participants enrolled into the Strategies for Management of Antiretroviral Therapy study, who subsequently died, and 284 matched controls, were assayed for levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/proinflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death.
Higher plasma levels of proinflammatory cytokines (interleukin-6 and tumour necrosis factor-α) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with interleukin-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of hepatitis C virus status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group.
Whereas plasma levels of interleukin-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs.
接受抗逆转录病毒治疗的HIV-1感染者的全因死亡率和严重非艾滋病事件（SNAEs）与白细胞介素-6产生增加有关，而白细胞介素-6的产生似乎是由单核细胞/巨噬细胞激活驱动的。与免疫激活相关的其他细胞因子或趋化因子的血浆水平也可能是死亡率和/或SNAEs风险增加的生物标志物。
对参与抗逆转录病毒治疗管理策略研究的142名随后死亡的参与者和284名匹配对照的基线血浆样本进行15种细胞因子和趋化因子水平的检测。分别分析细胞因子和趋化因子水平，并根据功能（先天/促炎反应、细胞转运和细胞激活/增殖）进行分组，以分析它们与随后死亡风险的关联。
促炎细胞因子（白细胞介素-6和肿瘤坏死因子-α）的血浆水平较高与全因死亡率增加相关，但在对潜在混杂因素进行调整的分析中，仅与白细胞介素-6的关联仍然存在。趋化因子CXCL8的血浆水平升高也与全因死亡率独立相关，与丙型肝炎病毒状态无关，但在对所有混杂因素进行调整的分析中则不然。相比之下，介导细胞激活/增殖的细胞因子血浆水平较高与较高的死亡风险无关，并且作为一组进行分析时显示出微弱的保护作用。
虽然白细胞介素-6的血浆水平是与HIV-1感染个体全因死亡率相关的细胞因子失调最具信息价值的生物标志物，但评估CXCL8的血浆水平可能会提供有关死亡原因以及可能的SNAEs的信息。
