Modulation of immune response by the acute and chronic exposure to high altitude.
OBJECTIVE
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.
Facco
Monica
M
Padua University School of Medicine, Department of Clinical and Experimental Medicine, Clinical Immunology Branch, Padova, Italy.
Zilli
Chiara
C
Siviero
Marta
M
Ermolao
Andrea
A
Travain
Giuseppe
G
Baesso
Ilenia
I
Bonamico
Sondra
S
Cabrelle
Anna
A
Zaccaria
Marco
M
Agostini
Carlo
C
D000328:Adult; D000531:Altitude; D017252:CD3 Complex / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007694:Killer Cells, Natural / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000097:blood; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism
D017252:CD3 Complex; D015704:CD4 Antigens; C515187:CXCR3 protein, human; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma