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  • Title: High Altitude and Acute Mountain Sickness and Changes in Circulating Endothelin-1, Interleukin-6, and Interleukin-17a.
    Author: Boos CJ, Woods DR, Varias A, Biscocho S, Heseltine P, Mellor AJ.
    Journal: High Alt Med Biol; 2016 Mar; 17(1):25-31. PubMed ID: 26680502.
    Abstract:
    INTRODUCTION: Hypoxia induces an inflammatory response, which is enhanced by exercise. High altitude (HA) leads to endothelial activation and may be proinflammatory. The relationship between endothelial activation, inflammation, and acute mountain sickness (AMS) and its severity has never been examined. METHODS: Forty-eight trekkers were studied during a progressive trek at 3833, 4450, and 5129 m at rest postascent (exercise), and then again at rest 24 hours later. Twenty of the subjects were also tested at rest pre- and postexercise at sea level (SL) at 6 weeks preascent. We examined plasma levels of the interleukin 6 (IL-6), 17a (IL-17a), and endothelin-1 (ET-1) along with oxygen saturation (SpO2) and Lake Louise scores (LLS). RESULTS: ET-1 (5.7 ± 2.1 vs. 4.3 ± 1.9 pg/mL; p < 0.001), IL-6 (3.3 ± 3.3 vs. 2.4 ± 2.3 pg/mL; p = 0.007), and IL-17a (1.3 ± 3.0 vs. 0.46 ± 0.4 pg/mL; p < 0.001) were all overall significantly higher at HA versus SL. There was a paired increase in ET-1 and IL-6 with exercise versus rest at SL, 3833, 4450, and 5129 m (p < 0.05). There was a negative correlation between LLS and SpO2 (r = -0.32; 95% confidence interval [CI] -0.21 to -0.42; p < 0.001) and a positive correlation between LLS and IL-6 (r = 0.16; 0.0-0.27; p = 0.007) and ET-1 levels (r = 0.29; 0.18-0.39; p < 0.001. Altitude, ET-1, IL-6, and SpO2 were all univariate predictors of AMS. On multivariate analysis, ET-1 (p = 0.002) and reducing SpO2 (p = 0.02) remained as the only independent predictors (overall r(2) = 0.16; p < 0.001) of AMS. ET-1 (p = 03) and SpO2 were (p = 0.01) also independent predictors of severe AMS (overall r(2) = 0.19; p < 0.001). CONCLUSIONS: HA leads to endothelial activation and an inflammatory response. The rise in ET-1 and IL-6 is heavily influenced by the degree of exercise and hypoxia. ET-1 is an independent predictor of both AMS and its severity.
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