IL-2, IL-17A and TNF-α hold potential as biomarkers for predicting acute mountain sickness prior to ascent

Background: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes. Methods: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity. Results: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n =17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-alpha at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-alpha and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.. Conclusion: We posited that the levels of TNF-alpha, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude. New & noteworthy: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-alpha could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m.