Excessive Iron Availability Caused by Disorders of Interleukin-10 and Interleukin-22 Contributes to High Altitude Polycythemia.
Excessive Iron Availability Caused by Disorders of Interleukin-10 and Interleukin-22 Contributes to High Altitude Polycythemia.
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白细胞介素 10 和白细胞介素 22 疾病引起的铁利用率过高会导致高原红细胞增多症
DOI：
10.3389/fphys.2018.00548
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发表时间：
2018
影响因子：
4
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Liu YS;Huang H;Zhou SM;Tian HJ;Li P
背景资料：由于高原红细胞增多症（HAPC）的发病机制尚不清楚，本研究旨在探讨铁代谢异常是否参与了HAPC的发病过程及其可能的病因。研究方法：我们检测了20名海平面健康志愿者、36名健康高原移民和33名HAPC患者的血清铁、总铁结合力、可溶性转铁蛋白受体（sTfR）、铁蛋白和铁调素以及促红细胞生成素（EPO）和炎症相关细胞因子水平。将小鼠暴露于海拔5,000 m的模拟低氧环境4周，给予外源性铁或细胞因子干预，检测外周血和骨髓铁相关血液学指标。同时观察了某些细胞因子对造血细胞的体外作用。结果：长期居住在高原地区的人铁动员和利用能力增强。值得注意的是，与健康的高海拔移民相比，HAPC患者的铁蛋白中的铁储存和血液中的有效铁均升高。相关性分析表明，铁调素的降低可能与HAPC铁利用率的提高有关，白细胞介素（IL）-10和IL-22的降低与铁调素的降低显著相关。动物实验结果证实，一定程度的铁冗余可促进缺氧小鼠骨髓红细胞生成和外周血红细胞生成，降低IL-10和IL-22通过影响hepcidin的表达而促进缺氧过程中的铁动员。结论：这些数据首次表明，由IL-10和IL-22紊乱引起的可获得的铁过量参与了一些HAPC患者的发病机制。铁清除和免疫调节对预防和治疗HAPC的潜在益处值得进一步研究。
Background: Because the pathogenesis of high altitude polycythemia (HAPC) is unclear, the aim of the present study was to explore whether abnormal iron metabolism is involved in the pathogenesis of HAPC and the possible cause. Methods: We examined the serum levels of iron, total iron binding capacity, soluble transferrin receptor (sTfR), ferritin, and hepcidin as well as erythropoietin (EPO) and inflammation-related cytokines in 20 healthy volunteers at sea level, 36 healthy high-altitude migrants, and 33 patients with HAPC. Mice that were exposed to a simulated hypoxic environment at an altitude of 5,000 m for 4 weeks received exogenous iron or intervention on cytokines, and the iron-related and hematological indices of peripheral blood and bone marrow were detected. The in vitro effects of some cytokines on hematopoietic cells were also observed. Results: Iron mobilization and utilization were enhanced in people who had lived at high altitudes for a long time. Notably, both the iron storage in ferritin and the available iron in the blood were elevated in patients with HAPC compared with the healthy high-altitude migrants. The correlation analysis indicated that the decreased hepcidin may have contributed to enhanced iron availability in HAPC, and decreased interleukin (IL)-10 and IL-22 were significantly associated with decreased hepcidin. The results of the animal experiments confirmed that a certain degree of iron redundancy may promote bone marrow erythropoiesis and peripheral red blood cell production in hypoxic mice and that decreased IL-10 and IL-22 stimulated iron mobilization during hypoxia by affecting hepcidin expression. Conclusion: These data demonstrated, for the first time, that an excess of obtainable iron caused by disordered IL-10 and IL-22 was involved in the pathogenesis of some HAPC patients. The potential benefits of iron removal and immunoregulation for the prevention and treatment of HAPC deserve further research.
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影响因子：
3.7
作者：
Huang H;Lamikanra AA;Alkaitis MS;Thézénas ML;Ramaprasad A;Moussa E;Roberts DJ;Casals-Pascual C
通讯作者：
Casals-Pascual C
影响因子：
3.7
作者：
Lu S;Natarajan SK;Mott JL;Kharbanda KK;Harrison-Findik DD
通讯作者：
Harrison-Findik DD
影响因子：
30.8
作者：
Kautz L;Jung G;Valore EV;Rivella S;Nemeth E;Ganz T
通讯作者：
Ganz T
影响因子：
2.1
作者：
León-Velarde, F;Maggiorini, M;Zubieta-Calleja, G
通讯作者：
Zubieta-Calleja, G
影响因子：
4.4
作者：
Budda, Scott A.;Girton, Alanson;Zenewicz, Lauren A.
通讯作者：
Zenewicz, Lauren A.