Abstract
Acute Mountain Sickness, Inflammation, and Permeability: New Insights From a Blood Biomarker Study
The authors of this article investigated the link between vasogenic edema associated with acute mountain sickness (AMS). One contributing factor to the development of vasogenic edema may be the disruption of the blood-brain barrier. Numerous mediators of inflammation and angiogenesis known to cause disruption of the blood-brain barrier can be modulated by hypoxia. This experimental study seeks to identify whether circulating biomarkers known to influence blood-brain barrier function are also related to AMS.
Twenty healthy volunteers (17 men and 3 women) were exposed to 4875 m in a hypobaric chamber. They participated in 3 separate trials, distinguished by pretreatment with placebo, acetazolamide, or dexamethasone using a randomized, double-blinded, placebo-controlled crossover design. Venous blood was sampled at time points including 15 hours before, 0 hours, 0.5 hours, 4 hours, and 9 hours. Measurements included antiinflammatory biomarkers interleukin (IL)-1 receptor agonist (IL-1RA), IL-4, IL-10, heat shock protein (HSP)-70, adrenomedullin, proinflammatory biomarkers IL-6, IL-8, IL-2, IL-1β, substance P, macrophage inflammatory protein-1β, vascular endothelial growth factor, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and serum matrix metalloproteinase-9. The AMS symptoms were evaluated using the Lake Louise Score (LLS).
Subjects with lower LLS had higher IL-1RA, HSP-70, and adrenomedullin compared with higher scoring AMS subjects. Acetazolamide raised IL-1RA and HSP-70 compared with placebo in higher scoring AMS subjects. Dexamethasone also increased HSP-70 and adrenomedullin in higher scoring AMS subjects. Macrophage inflammatory protein-1β was higher in higher scoring AMS subjects than lower scoring AMS subjects after 4 hours of hypoxia—dexamethasone minimized this difference. Other biomarkers did not appear to be related to AMS. Lower scoring AMS subjects demonstrated a marked antiinflammatory and antipermeability response that may have prevented downstream pathophysiological events leading to AMS. Conversely, higher scoring AMS subjects did not demonstrate an exaggerated inflammatory response.
(J Appl Physiol. 2011;111:392–399) CG Julian, AW Subudhi, MJ Wilson, et al
Prepared by Derek Nusbaum, MD, Baylor College of Medicine Internal Medicine Resident, Houston, TX, USA.