The Time Course of Endogenous Erythropoietin, IL-6, and TNFα in Response to Acute Hypoxic Exposures

Erythropoietin (EPO) rapidly decreases on return to sea level (SL) after chronic altitude exposure. Acute hypoxia may provide an additional stimulus to prevent the decline in EPO. Proinflammatory cytokines, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) have been shown to inhibit EPO production. Optimal normobaric hypoxic exposure has not been established; therefore, investigation of methods eliciting the greatest response in EPO to limit physiological stress is required. Eight men (age 27 ± 4 years, body mass 77.5 ± 9.0 kg, height 179 ± 6 cm) performed four passive exposures to different normobaric hypoxic severities [FiO : 0.209 (SL), FiO : ~0.135 (3600 m), FiO : ~0.125 (4200 m) and FiO : ~0.115 (4800 m)] in a hypoxic chamber for 2 h. Venous blood was drawn pre-exposure and then at 1, 2, 4, 6, and 8 h to determine EPO concentration ([EPO]), IL-6, and TNFα. During 4200 and 4800 m, [EPO] increased from 5.9 ± 1.5 to 8.1 ± 1.5 mU/mL (P = 0.009) and 6.0 ± 1.4 to 8.9 ± 2.0 mU/mL (P = 0.037), respectively, with [EPO] increase peaking at 4 h (2 h post-exposure). There were no differences in IL-6 or TNFα during or post-exposure. Increased [EPO] was found 2 h post hypoxic exposure as result of 2 h of normobaric hypoxia ≥4200 m. There was no dose-response relationship in [EPO] between simulated hypoxia severities.