Reduced inflammatory and phagocytotic responses following normobaric hypoxia exercise despite evidence supporting greater immune challenge

Garrett W Hill, Trevor L Gillum, Ben J Lee, Phebe A Romano, Zach J Schall, Matthew R Kuennen

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


This study examined changes in immune markers following sustained treadmill exercise in normobaric hypoxia. Ten subjects performed 1 h of treadmill exercise (65% maximal oxygen uptake) under normoxic (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and normobaric hypoxic (HYP: FIO2 = 13.5%) conditions. Blood samples, collected before, after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise, were assayed for plasma cytokines (interleukin (IL)-1RA/IL-1β/IL-8/tumor necrosis factor alpha (TNF-α)) and markers of leukocyte activation (macrophage inflammatory protein-1β (MIP-1β)/myeloperoxidase (MPO)/soluble intercellular adhesion molecule-1 (sICAM-1)) using ELISA. Pro- to anti-inflammatory cytokine ratios (TNF-α/IL-1RA; IL-1β/IL-1RA) were calculated. Peripheral blood mononuclear cells (PBMC) were analyzed for changes in inflammatory status (phosphorylated nuclear factor kappa B/nuclear factor kappa B) using Western Blot. Data were analyzed with 2-way (condition × time) repeated-measure ANOVAs with Newman-Keuls post hoc tests. MIP-1β was elevated at 1-Post HYP exercise (+11%; p < 0.01) but did not increase following exercise in NORM. TNF-α/IL-1RA and IL-1β/IL-1RA ratios were both reduced (p < 0.05) following HYP exercise (-16% and -52%, respectively, at 1-Post and -7% and -32%, respectively, at 4-Post). IL-8 increased (p < 0.05) at Post and 1-Post NORM (+33% and +57%, respectively) and HYP (+60% and +83%, respectively) exercise, but was not different between conditions (p > 0.05). Interestingly, plasma sICAM-1 did not increase (p > 0.05) following NORM exercise but was increased (p < 0.05) at Post (+17%), 1-Post (+16%), and 4-Post (+14%) HYP exercise. There was also a delayed peak in plasma MPO concentrations following HYP exercise and PBMC exhibited a reduced (p < 0.05) inflammatory capacity at Post (-38%) and 1-Post (-49%). Novelty Following HYP exercise, participants exhibited (i) circulatory bias towards anti-inflammation; (ii) elevated sICAM; (iii) delayed peak in plasma MPO; and (iv) diminished inflammatory response in PBMC. Collectively, these data suggest immunosuppression. This is undesirable, given that elevated MIP-1β (reported here) and elevated intestinal fatty acid binding protein (reported previously) both suggest higher lipopolysaccharide concentrations following HYP exercise.

Original languageEnglish
Pages (from-to)628-640
Number of pages13
JournalApplied Physiology, Nutrition, and Metabolism
Issue number6
Early online date21 Nov 2019
Publication statusPublished - Jun 2020
Externally publishedYes


  • Altitude
  • Cytokines
  • Exercise immunology
  • Gastrointestinal barrier
  • Immune suppression
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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