Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels

• Published in: High altitude medicine & biology Vol. 19; no. 3; p. 249
• Main Authors: Lundeberg, Jenny, Feiner, John R, Schober, Andrew, Sall, Jeffrey W, Eilers, Helge, Bickler, Philip E
• Format: Journal Article
• Language: English
• Published: United States 01.09.2018
• Subjects: Acclimatization - drug effects; Adult; Altitude Sickness - blood; Altitude Sickness - drug therapy; Altitude Sickness - physiopathology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Brain - metabolism; Cytokines - blood; Cytokines - genetics; Double-Blind Method; Female; Gene Expression - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - blood; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Heart Rate - drug effects; Humans; Ibuprofen - pharmacology; Ibuprofen - therapeutic use; Interleukin-10 - blood; Interleukin-10 - genetics; Interleukin-1beta - blood; Interleukin-1beta - genetics; Interleukin-6 - blood; Interleukin-6 - genetics; Interleukin-8 - blood; Interleukin-8 - genetics; Male; Middle Aged; Muscle, Skeletal - metabolism; Oximetry; Oxygen - blood; Oxygen - metabolism; RNA, Messenger - blood; Treatment Failure; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Young Adult; anti-inflammatory agents nonsteroidal; altitude; cytokines; acclimatization; acute mountain sickness; altitude sickness
• ISSN: 1557-8682
• DOI: 10.1089/ham.2017.0144

Lundeberg, Jenny, John R. Feiner, Andrew Schober, Jeffrey W. Sall, Helge Eilers, and Philip E. Bickler. Increased cytokines at high altitude: lack of effect of ibuprofen on acute mountain sickness, physiological variables or cytokine levels. High Alt Med Biol. 19:249-258, 2018. There is no consensus on the role of inflammation in high-altitude acclimatization. To determine the effects of a nonsteroidal anti-inflammatory drug (ibuprofen 400 mg every 8 hours) on blood cytokines, acclimatization, acute mountain sickness (AMS, Lake Louise Score), and noninvasive oxygenation in brain and muscle in healthy volunteers. In this double-blind study, 20 volunteers were randomized to receive ibuprofen or placebo at sea level and for 48 hours at 3800 m altitude. Arterial, brain, and leg muscle saturation with near infrared spectroscopy, pulse oximetry, and heart rate were measured. Blood samples were collected for cytokine levels and cytokine gene expression. All of the placebo subjects and 8 of 11 ibuprofen subjects developed AMS at altitude (p = 0.22, comparing placebo and ibuprofen). On arrival at altitude, the oxygen saturation as measured by pulse oximetry (S O ) was 84.5% ± 5.4% (mean ± standard deviation). Increase in blood interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels occurred comparably in the placebo and ibuprofen groups (all not significant, univariate test by Wilcoxon rank sum). Increased IL-6 was associated with higher AMS scores (p = 0.002 by Spearman rank correlation). However, we found no difference or association in AMS score and blood or tissue oxygenation between the ibuprofen and placebo groups. We found that ibuprofen, at the package-recommended adult dose, did not have a significant effect on altitude-related increases in cytokines, AMS scores, blood, or tissue oxygenation in a population of healthy subjects with a high incidence of AMS.