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High Altitude and Acute Mountain Sickness and Changes in Circulating Endothelin-1, Interleukin-6, and Interleukin-17a

Lookup NU author(s): Dr David Woods, Dr Adrian Mellor


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Boos, Christopher John, David R. Woods, Andrea Varias, Sheryl Biscocho, Peter Heseltine, and Adrian J. Mellor. High altitude and acute mountain sickness and changes in circulating endothelin-1, interleukin-6, and interleukin-17a. High Alt Med Biol. 17:25-31, 2016.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 5129m 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 (SpO(2)) and Lake Louise scores (LLS). Results: ET-1 (5.7 +/- 2.1 vs. 4.3 +/- 1.9pg/mL; p<0.001), IL-6 (3.3 +/- 3.3 vs. 2.4 +/- 2.3pg/mL; p=0.007), and IL-17a (1.3 +/- 3.0 vs. 0.46 +/- 0.4pg/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 5129m (p<0.05). There was a negative correlation between LLS and SpO(2) (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 SpO(2) were all univariate predictors of AMS. On multivariate analysis, ET-1 (p=0.002) and reducing SpO(2) (p=0.02) remained as the only independent predictors (overall r(2)=0.16; p<0.001) of AMS. ET-1 (p=03) and SpO(2) 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.

Publication metadata

Author(s): Boos CJ, Woods DR, Varias A, Biscocho S, Heseltine P, Mellor AJ

Publication type: Article

Publication status: Published

Journal: High Altitude Medicine & Biology

Year: 2016

Volume: 17

Issue: 1

Pages: 25-31

Print publication date: 15/03/2016

Online publication date: 17/12/2015

Acceptance date: 05/11/2015

ISSN (print): 1527-0297

ISSN (electronic): 1557-8682

Publisher: Mary Ann Liebert, Inc. Publishers


DOI: 10.1089/ham.2015.0098


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