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

High Alt Med Biol. 2018 Sep;19(3):249-258. doi: 10.1089/ham.2017.0144. Epub 2018 Jun 20.


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.

Introduction: There is no consensus on the role of inflammation in high-altitude acclimatization.

Aims: 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.

Materials and methods: 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.

Results: 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 (SpO2) 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.

Conclusions: 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.

Keywords: acclimatization; acute mountain sickness; altitude; altitude sickness; anti-inflammatory agents nonsteroidal; cytokines.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 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, Non-Steroidal
  • CXCL8 protein, human
  • Cytokines
  • IL10 protein, human
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Oxygen
  • Ibuprofen