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Inflammatory gene expression during acute high-altitude exposure.
Kathy Pham1, Shyleen Frost1, Keval Parikh1
1Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA, USA.
The Journal of Physiology
|July 25, 2022
Summary
High-altitude exposure triggers inflammation and alters immune responses, potentially impacting acclimatization and altitude sickness. This study reveals early changes in inflammatory genes, including HMGB1, suggesting immune system sensitization.
Area of Science:
- Physiology
- Immunology
- Altitude Medicine
Background:
- Inflammation and hypoxia response pathways are crucial for high-altitude adaptation.
- Existing research shows increased inflammatory markers at high altitudes, but immune function changes and pathology links are unclear.
Purpose of the Study:
- To investigate alterations in the peripheral blood inflammatory profile during the initial 3 days of high-altitude acclimatization.
- To identify specific genes and pathways involved in the inflammatory response to acute hypoxia.
Main Methods:
- Unbiased transcriptomic analysis using RNA sequencing and NanoString technology.
- Analysis of peripheral blood samples from 15 healthy sea-level residents over 3 days at high altitude.
Main Results:
- Upregulation of inflammation-related genes, notably high mobility group box 1 (HMGB1), on day 1 of exposure.
- Enrichment of nuclear factor-κB and Toll-like receptor (TLR) signalling pathways.
- Association of FASLG and SMAD7 with acute mountain sickness and oxygen saturation.
Conclusions:
- Acute high-altitude exposure induces significant changes in inflammatory signalling pathways.
- The Toll-like receptor 4 (TLR4) pathway may be sensitized by high-altitude hypoxia.
- Immune regulation alterations may contribute to high-altitude pathologies and hypoxemia-related conditions.

