Pro- and Anti-Inflammatory Responses Following Active and Passive Ascent to 3600 m

Abstract

Lowlanders who develop acute mountain sickness (AMS) following rapid ascent to high altitude (HA) demonstrate increased levels of both pro-inflammatory (tumor necrosis factor α (TNFα), Interleukin (IL)- 1β, IL-6, IL-8, and IL-17α) and anti-inflammatory biomarkers (IL-10 and IL-1 receptor agonist; IL-1ra). Whether ascending by self-locomotion (i.e., active ascent) modulates these pro- and anti-inflammatory cytokine responses at HA is unknown. We hypothesized a greater pro-inflammatory response in the AMS-susceptible group following active ascent. To test this hypothesis, 78 healthy Soldiers (mean±SD; age, 26±5yr) were tested at baseline residence (BLR), transported to Taos, NM (2845m), then hiked (n=39) or were driven (n=39) to HA (3600m), and stayed for 4 days. AMS-Cerebral factor score (AMS-C) was assessed using the Environmental Symptoms Questionnaire (ESQ) at HA twice on day 1 (HA1). If AMS-C was ≥0.7 at either assessment, individuals were categorized as AMS-susceptible (AMS+; n=24); others were AMS-resistant (AMS−; n=54). Fasting blood samples were taken at 06:00 at BLR, HA2, HA3 and HA4 and analyzed to determine cytokine (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-17α, and IL-1ra) responses following the initial hypoxic insult. Blood values (pg/mL) were log-transformed and adjusted for plasma volume changes from BLR to HA. The active group expended a greater ( p<0.05) amount of energy (745±435 kcal) than the passive group (55±10 kcal) during ascent. There were no differences in biomarkers between ascent groups, so data were combined. In the AMS-susceptible group, IL-17α increased ( p<0.05) from BLR to HA2 (63.3±8.8 to 73.1±8.8, p=0.002) and remained increased at HA3 (70.1±8.8) and HA4 (73.1±8.8). In the AMS-resistant group, IL-17α did not change from BLR to any of the days at HA. Independent of AMS susceptibility, the anti-inflammatory marker IL-1ra increased from BLR to HA2 (63.5±11.4 to 89.9±11.4, p=0.013) and then fell back down to BLR values on HA3 (70.4±11.4, p=0.560) and HA4 (71.8±11.4, p=0.537). When all days were combined, TNFα (+15%, p=0.036), IL-6 (+50%, p=0.042), and IL-10 (+36%, p=0.040) were increased in the AMS-susceptible compared to the AMS-resistant group. IL-1β and IL-8 did not change ( p>0.05) from BLR to any time point at HA in either group. In conclusion, both a robust pro- (TNFα, IL-6, IL-17α) and anti-inflammatory (IL-10) response occurred at HA in those susceptible to AMS most likely due to inflammation following the initial hypoxic insult followed quickly by an anti-inflammatory response. However, ascent strategy on HA1 had no impact on pro- or anti-inflammatory cytokines on days 2-4 at HA. Authors’ views not offcial U.S. Army or DoD policy. Funding: USAMRDC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.