title: High Altitude and Acute Mountain Sickness and Changes in Circulating Endothelin-1, Interleukin-6, and Interleukin-17a.
abstract: BACKGROUND
  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.
authors.affiliation: 1 Department of Cardiology, Poole Hospital NHS Foundation Trust , Poole, Dorset, United Kingdom .|2 Department of Postgraduate Medical Education, Bournemouth University , Bournemouth, United Kingdom .
authors.forename: Christopher John
authors.initials: CJ
authors.lastname: Boos
authors.affiliation: 3 Northumbria and Newcastle NHS Trusts, Wansbeck General and Royal Victoria Infirmary , Newcastle, United Kingdom .|4 Defence Medical Services , Lichfield, United Kingdom .|5 University of Newcastle , Newcastle upon Tyne, United Kingdom .|6 Leeds Beckett University , Leeds, United Kingdom .
authors.forename: David R
authors.initials: DR
authors.lastname: Woods
authors.affiliation: 6 Leeds Beckett University , Leeds, United Kingdom .
authors.forename: Andrea
authors.initials: A
authors.lastname: Varias
authors.affiliation: 6 Leeds Beckett University , Leeds, United Kingdom .
authors.forename: Sheryl
authors.initials: S
authors.lastname: Biscocho
authors.affiliation: 6 Leeds Beckett University , Leeds, United Kingdom .
authors.forename: Peter
authors.initials: P
authors.lastname: Heseltine
authors.affiliation: 4 Defence Medical Services , Lichfield, United Kingdom .|7 Singulex, Inc. , Alameda, California.|8 James Cook University Hospital , Middlesbrough, United Kingdom .
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mellor
mesh_terms: D000208:Acute Disease; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood*; D001838:Bolivia; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009051:Mountaineering / Q000502:physiology; D012146:Rest / Q000502:physiology
chemical_list: D019332:Endothelin-1; C508717:IL17A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6
keywords: acute mountain sickness; endothelin; exercise; high altitude; inflammation; interleukin