Abstract
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.
Highlights
As a normal physiological compensatory response to a hypoxic environment, high-altitude (HA) migrants often experience increases in their number of red blood cells (RBCs), which improve the oxygen-carrying capacity of the blood (Windsor and Rodway, 2007)
Compared with the HA healthy men at the same elevation, high altitude polycythemia (HAPC) patients with excessive erythrocytosis exhibited further increases in serum iron and soluble transferrin receptor (sTfR) as well as total iron binding capacity (TIBC) related to iron transportation, revealing sufficient iron availability
Further analysis among the 69 HA migrants showed that serum available iron was positively associated with hemoglobin content, which is an indicator reflecting the degree of erythrocytosis
Summary
As a normal physiological compensatory response to a hypoxic environment, high-altitude (HA) migrants often experience increases in their number of red blood cells (RBCs), which improve the oxygen-carrying capacity of the blood (Windsor and Rodway, 2007). Some migrants (∼10–40%, depending on the altitude) have excessive erythropoiesis after several months or years, which results in high altitude polycythemia (HAPC), known as chronic mountain sickness (CMS) or Monge’s disease (Negi et al, 2013). It is necessary to explore other mechanisms that may be involved in erythrocytosis at high altitudes. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
