Modulation of immune response by the acute and chronic exposure to high altitude.

PURPOSE: The chronic exposure at high altitude (HA) represents an ideal model for evaluating the in vivo effects of hypobaric hypoxia. Taking advantage of the EV-K2-CNR Pyramid, this study was designed to evaluate whether acute and chronic hypoxia differently modulates the in vivo immune responses. METHODS: The study includes 13 healthy female moderately active volunteers participating to the Italian HA project EV-K2-CNR. Peripheral blood lymphocytes, collected at sea level and at HA in the Pyramid Laboratory of CNR, Nepal (5050 m), were immunologically characterized by flow cytometry and a series of molecular and functional analyses. RESULTS: Flow cytometric analyses showed that: a) CD3+ T lymphocytes significantly decreased during both acute and chronic exposure to HA, b) T-cell fall was totally due to CD4+ T-cell reduction, c) B lymphocytes were not influenced by the exposure to HA, and d) natural killer (NK) cells significantly increased during acute and chronic exposure. The evaluation of the Th1/Th2 pattern demonstrated a significant decrease of the expression of the Th1 cytokine interferon-gamma (IFN-gamma) by circulating T cells during acute and chronic exposure to HA. The expression by T cells of CXCR3, a chemokine receptor typically expressed by Th1/Tc1 cells, paralleled the decrease of IFN-gamma. On the contrary, the expression of IL-4 was not conditioned by the exposure to HA. Finally, functional studies showed a significant reduction of the proliferative activity in response to mitogen (PHA) both in acute and chronic HA exposure. Despite the increased number of NK cells, NK cytotoxic activity was not influenced by the HA exposure. CONCLUSIONS: Our results indicate that the in vivo exposure to HA leads to an impairment of the homeostatic regulation of Th1/Th2 immune balance that potentially could favor long-term immunological alterations and increase the risk of infections.

Decreased serum leptin levels during prolonged high altitude exposure.

Circulating leptin concentrations are shown to be influenced not only by hormones, but also by body weight and energy balance. High altitude (HA) exposure induces a daily negative energy balance and stress hormone activation. The aim of our study was to evaluate leptin concentration during both acute and prolonged HA exposure and its correlations with some metabolic and hormonal parameters. Twelve males were studied during a stay at HA (15-20 days at 5,050 m). Blood samples for serum leptin, plasma insulin and 24-h urinary epinephrine (E) and norepinephrine (NE) were collected at sea level (SL), at the arrival at HA (A) and after 12-16 days (C) of stay. Symptoms of Acute Mountain Sickness (AMS) were evaluated using the Lake Louise score and the results showed there was no relationship with leptin concentrations. During the stay, both body mass index and leptin levels significantly decreased in both groups [leptin from 1.88 (1.12) to 1.21 (1.04) ng/ml, P<0.008, in A; and to 1.06 (0.74) ng/ml, P<0.003, in C]. Acute HA exposure induced a clear-cut significant increase of NE ( P<0.001 in A, P<0.003 in C) while E and insulin levels were unchanged in both phases. Moreover, a significant correlation between leptin and NE absolute values, and leptin and insulin variations was found ( r 0.359, P<0.034 and r=0.560, P<0.007, respectively). Exposure to HA induces a decrease in fasting serum leptin concentrations in men. These changes are not linked to symptoms of AMS but to hormonal and energy balance variations, suggesting that leptin is involved in the endocrine and metabolic adaptations occurring during HA exposure.