High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein

Cytokine. 2000 Mar;12(3):246-52. doi: 10.1006/cyto.1999.0533.


Hypoxic pulmonary vasoconstriction is associated with but may not be sufficient for the development of high-altitude pulmonary oedema (HAPO). Hypoxia is known to induce an inflammatory response in immune cells and endothelial cells. It has been speculated that hypoxia-induced inflammatory cytokines at high altitude may contribute to the development of HAPO by causing capillary leakage in the lung. We were interested if such an inflammatory response, possibly involved in a later development of HAPO, is detectable at high altitude in individuals without HAPO. We examined the plasma levels of interleukin 6 (IL-6), interleukin 1 receptor antagonist (IL-1ra) and C-reactive protein (CRP) in two independent studies: study A, Jungfraujoch, Switzerland, three overnight stays at 3458 m, n=12; study B: Capanna Regina Margherita, Italy, 3 overnight stays at 3647 m and one overnight stay at 4559 m, n=10. In both studies, probands showed symptoms of acute mountain sickness but no signs of HAPO. At the Jungfraujoch, IL-6 increased from 0.1+/-0.03 pg/ml to 2. 0+/-0.5 pg/ml (day 2, P=0.03), IL-1ra from 101+/-21 to 284+/-73 pg/ml (day 2, P=0.01), and CRP from 1.0+/-0.4 to 5.8+/-1.5 micrograms/ml (day 4, P=0.01). At the Capanna Margherita, IL-6 increased from 0. 5+/-0.2 pg/ml to 2.0+/-0.8 pg/ml (P=0.02), IL-1ra from 118+/-25 to 213+/-28 pg/ml (P=0.02), and CRP from 0.4+/-0.03 to 3.5+/-1.1 micrograms/ml (P=0.03). IL-8 was below the detection limit of the ELISA (<25 pg/ml) in both studies. The increase of IL-6 and IL-1ra in response to high altitude was delayed and preceded the increase of CRP. We conclude that: (1) circulating IL-6, IL-1ra and CRP are upregulated in response to hypobaric hypoxic conditions at high altitude, and (2) the moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence and the kinetics of high altitude-induced cytokines found in this study support the hypothesis that inflammation is involved in the development of HAPO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Altitude
  • Altitude Sickness / blood*
  • Altitude Sickness / metabolism
  • C-Reactive Protein / metabolism*
  • Female
  • Humans
  • Inflammation / etiology
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6 / blood*
  • Male
  • Oxygen / metabolism*
  • Pulmonary Edema / blood*
  • Pulmonary Edema / metabolism
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Receptors, Interleukin-1 / metabolism
  • Sialoglycoproteins / biosynthesis*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • C-Reactive Protein
  • Oxygen