Hormonal influences on the immune function during acute and chronic high altitude exposure

We recently observed that acute and chronic high altitude (HA) exposure can modify number and function of immune cells, leading to a disruption in the homeostatic regulation of Th1/Th2 immune responses1. The autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis have been demonstrated to play a critical role in mediating many physiological adaptations to HA exposure. Both these systems are also known to modulate the immune function through cortisol (C) and catecholamines secretion. AIM To evaluate possible relationships between stress hormones activation and immunological parameters during acute and chronic HA exposure. METHODS 13 moderately active healthy women (age 21.3±3.1yr) reached after 5 days of trekking the Pyramid Laboratory at 5,050 m (Lobuche, Nepal) where they spent 21 days. Before and after HA exposure (SL1 and SL2), and in the first (P1) and 21th day spent at HA (P2), we collected blood samples for peripheral white blood cells, their subsets, IFN-γ, IL-4 and 24-h urine samples for norepinephrine (NE) epinephrine (E) and C. RESULTS During HA exposure, total lymphocytes, compared to SL1 value significantly decreased at P1, rose at P2 and returned to their basal values at SL2 (SL1 2.0±0.5x103/ml, P1 1.3±0.6, p<.005; P2 2.4±0.6, p<.005, SL2 1.6±0.6, p=n.s). In particular CD3+ T lymphocytes percentage fell respect to SL1, owing to a significant CD4+ T-cell fall (from 50.4±4.2 to 32.1±8.2, p<.001 at P1, and to 32.0±8.8 p<.01 at P2). The percent of Natural Killer cells (NK) significantly increased both at P1 and at P2 (CD16+: SL1 14.2±4.5, P1 25.0±2.6 p<.001, P2 21.4±4.6, p<.001 and CD56+: SL1 12.5±5.2, P1 28.2±5.7 p<.001, P2 24.6±3.4, p<.001) while returned to basal values at SL2. From a functional viewpoint, the expression of IFN-γ (a typical Th1/Tc1 cytokine) significantly decreased at P1 and P2 respect to SL1 values (Mean Fluorescence Intensity: 32.0±8.5 at SL1, 19.2±5.5, p<.005 at P1, and 7.0±3.7, p<.005 at P2), whereas IL-4 (a typical Th2/Tc2 cytokine) didn’t change. Among stress hormones, only NE significantly increased at P1 and at P2 respect to SL values (from 178.6±69.2nmol/24h to 498.3±225.2 p<.001 and to 520.8±282.6 p<.005, respectively), E showed only a positive trend (p=.08), while C, respect to SL1 raised significantly at P1 (p<.01) and P2 (p<.05), but showed significantly lower values at SL2 (p<.005). CD3+, CD4+ and NK cells demonstrated a large and significant correlation with NE and C, (R ranged between 0.4 and 0.6), however only NE levels well correlated with IFN-γ expression (R=.537, p<.005). CONCLUSIONS Our data suggest that the ANS and the HPA axis played a central role on the cellular and functional immunologic adaptations observed at HA. Specifically, the ANS activity, through NE secretion, may be one of the mechanisms responsible for the impairment of the Th1/Th2 immune balance, as demonstrated in other stress conditions. 1Facco M., et al. Med Sci Sports Exerc 2005 May;37(5):768-74.