Lu Hui, Wang Rong, Li Wenbin, Xie Hua, Wang Chang, Hao Ying, Sun Yuhuan, Jia Zhengping
Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, China.
Eur Cytokine Netw. 2016 Nov 1;27(4):90-96. doi: 10.1684/ecn.2016.0383.
Extensive studies have been performed on acute mountain sickness (AMS), but biomarkers predicting AMS are lacking. Presently, the mainstay methods to identify AMS biomarkers include proteomic and genetic methods at high altitudes or in hypoxic simulated chambers. In the present study, we compared plasma cytokine profiles between AMS-susceptible individuals and AMS-resistant individuals at low altitude by cytokine array analysis. In total, 75 differentially expressed cytokines were identified between AMS-susceptible individuals and AMS-resistant individuals, most involved in inflammation. A quantifiable human custom cytokine antibody array was then used to further test results of cytokine array analysis. Compared to AMS-resistant individuals, the level of insulin-like growth factor binding protein 6 (IGFBP-6) was significantly lower in AMS-susceptible individuals (37,318.99 ± 23,493.11 pg/mL and 25,665.38 ± 25,691.29 pg/mL, respectively; P = 0.04). Conversely, the levels of serum amyloid A1 (SAA1), dickkopf WNT signaling pathway inhibitor 4 (Dkk4), and interleukin 17 receptor A (IL-17RA) were significantly higher in AMS-susceptible individuals than in AMS-resistant individuals (SAA1: 4,069.69 ± 2,502.93 pg/mL vs. 2,994.98 ± 2,295.91 pg/mL, P = 0.05; Dkk4: 2,090.00 ± 2,094.89 pg/mL vs. 1,049.88 ± 1,690.93 pg/mL, P = 0.07; IL-17RA: 11.52 ± 8.33 pg/mL vs. 8.67 ± 6.22 pg/mL, P = 0.08). Although further in-depth research is required to examine the possible role of these cytokines in the development of AMS, these four cytokines may be of use in predicting AMS-susceptibility in a low-altitude environment.
针对急性高原病（AMS）已经开展了广泛研究，但目前仍缺乏预测AMS的生物标志物。目前，识别AMS生物标志物的主要方法包括在高海拔地区或低氧模拟舱内采用蛋白质组学和遗传学方法。在本研究中，我们通过细胞因子阵列分析比较了低海拔地区AMS易感个体和AMS耐受个体之间的血浆细胞因子谱。总共在AMS易感个体和AMS耐受个体之间鉴定出75种差异表达的细胞因子，其中大多数与炎症相关。随后使用可定量的人类定制细胞因子抗体阵列进一步验证细胞因子阵列分析的结果。与AMS耐受个体相比，AMS易感个体中胰岛素样生长因子结合蛋白6（IGFBP-6）水平显著降低（分别为37,318.99±23,493.11 pg/mL和25,665.38±25,691.29 pg/mL；P = 0.04）。相反，AMS易感个体中血清淀粉样蛋白A1（SAA1）、 dickkopf WNT信号通路抑制剂4（Dkk4）和白细胞介素17受体A（IL-17RA）的水平显著高于AMS耐受个体（SAA1：4,069.69±2,502.93 pg/mL对2,994.98±2,295.91 pg/mL，P = 0.05；Dkk4：2,090.00±2,094.89 pg/mL对1,049.88±1,690.93 pg/mL，P = 0.07；IL-17RA：11.52±8.33 pg/mL对8.67±6.22 pg/mL，P = 0.08）。尽管需要进一步深入研究以探究这些细胞因子在AMS发生发展中的可能作用，但这四种细胞因子可能有助于在低海拔环境中预测AMS易感性。
