The time course of endogenous erythropoietin, IL-6, and TNFα in response to acute hypoxic exposures

Abstract

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. Pro-inflammatory 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 males (age 27±4 yrs, body mass 77.5±9.0 kg, height 179±6 cm) performed four passive exposures to different normobaric hypoxic severities [FiO2:0.209 (SL), FiO2:~0.135 (3,600 m), FiO2:~0.125 (4,200 m) and FiO2:~0.115 (4,800 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 erythropoietin concentration ([EPO]), IL-6 and TNFα. During 4,200 m and 4,800 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 4h (2h 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 ≥4,200 m. There was no dose-response relationship in [EPO] between simulated hypoxia severities.