Relationship between stress hormones and immune function at high altitude

We recently observed that acute and chronic high altitude (HA) exposure can modify number and function of immune cells. As environmental stress condition, hypobaric hypoxia increases hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity; both these systems have been demonstrated to modulate the immune function through cortisol and catecholamines secretion. PURPOSE: To evaluate possible relationships between stress hormones activation and immunological parameters during acute and chronic HA exposure. METHODS: 6 healthy moderately active women (mean age 20.6±1.3) reached after 5 days of trekking the Pyramid Laboratory at 5,050 m (Lobuche, Nepal) where stayed for 21 days. Before and after HA exposure (SL1 and SL2), and in the first (P1) and 21th day spent at HA (P2), blood samples for peripheral white blood cells and their subsets, and 24-h urine samples for norepinephrine (NE) epinephrine (E) and cortisol (C), were collected. RESULTS: During HA exposure (P1 and P2), total lymphocytes significantly decreased in P1 while returned to SL1 values in P2 (from 2.0±0.5x103/ml SL1 to 1.4·103±0.4x103/m P1, p<.05). In particular CD3+ T lymphocytes percentage fell respect to SL1 (from 72.8±6.8 to 54.2±12.4, p<.01 in P1, and to 54.5±12.5 p<.01 in P2), owing to a significant CD4+ T-cell fall (from 50.2±3.9 to 30.8±11.5, p<.01 in P1, and to 35.3±7.9 p<.01 in P2). The percent of Natural Killer cells (NK) (CD16+ and CD56+) significantly increased both in P1 and in P2 (from 15.5±4.4 to 25.2±2.4 p<.01, to 23.3±4.4, p<.01 and from 13.0±6.2 to 26.3±6.8 p<.01, to 21.8±2.7, p<.05, for CD18+ and CD56+, respectively). All these parameters were normalized in SL2, and not significantly different from SL1. Among stress hormones, only NE significantly increased in P1 and in P2 respect to SL values (from 127.4±15.6 to 581.9±219.8 p<.01 and to 737.0±263.5 p<.01, respectively), E showed only a positive trend (p=.08), while cortisol progressively raised reaching a significant increase in P2 (p<.01). CD3+, CD4+ and NK cells demonstrated a large and significant correlation with all three stress hormones, with the strongest correlations observed with NE (R ranged between 0.5 and 0.7). CONCLUSIONS: Acute and chronic HA exposure affect several cellular immunologic parameters. Their correlations with catecholamines levels suggest a role of sympathetic nervous system in the immune modulation observed during hypobaric hypoxia.