Suppression of plasma hepcidin by venesection during steady-state hypoxia.

Hepcidin inhibits iron uptake from the gut and release of iron from macrophages in the reticuloendothelial system. Suppression of plasma hepcidin occurs in lowlanders after ascent to high altitude, reflecting the increased iron demand for erythropoiesis, but the mechanism and primary stimulus for hepcidin suppression in this setting remains unclear. It has been suggested that hypoxia per se, possibly via the hypoxia-inducible factor family of transcription factors, provides a stimulus for transcriptional suppression of hepcidin. This is supported by the hepcidin suppression seen in patients with congenital upregulation of hypoxia-inducible factor proteins, even after correction for hemoglobin and iron status. However, others have argued that hepcidin suppression does not result from hypoxia directly, but rather from the hypoxia-induced increase in erythropoietic drive. Hepcidin levels are suppressed in patients with excessive ineffective erythropoiesis at sea level, although they remain normal in healthy high-altitude residents exposed to long-term hypoxia and in patients with polycythemia vera at sea