Operation Everest II: Alterations in the immune system at high altitudes

Abstract

We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneous in vitro and in vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemagglutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulated in vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft, in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of altered in vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested by in vitro immune assays of effector-cell function.

Implications of moderate altitude training for sea-level endurance in elite distance runners

“…Both in vivo and in vitro evidence suggests that hypobaric hypoxia decreases immunoreactivity, speci®cally by suppressing T-cell-mediated immunity (Meehan 1987(Meehan , 1988. Oxidative damage mediated by free radicals also increases at altitude (Simon-Schnass 1990;Vasankari et al 1997) which has implications for membrane integrity and energy metabolism.…”

Immune System

“…It is generally observed that this branch of immunity is only marginally affected by high altitude exposure [ 48 , 69 , 79 -81 ], although lymphopenia has been reported to occur with acute exposure to hypoxia [ 9 , 24 ] possibly as a result of the associated increase in cortisol. In the Operation Everest II study cited above, it was reported that no differences were found at any altitude in polyclonal B-cell function [ 48 ]. After 9 days at altitude, no differences in spontaneous or pokeweed mitogen (PWM)-stimulated IgA, IgG, or IgM production were found.…”

“…T-cell subsets carry out a variety of immunological functions including helper, suppressor, and cytotoxic (killing cells already infected with viruses and other intracellular pathogens). The literature clearly indicates that cell-mediated immunity and T lymphocyte function is the branch of the immune system most adversely affected by acute exposure to high altitude [ 48 ]. Several investigations involving human subjects suggest that acute exposure Fig.…”

“…This is likely related to the continued increase in SNS activity with acclimatization and the direct norepinephrine stimulation of the α-adrenergic pathway, as α-blockade completely abolishes this IL-6 response observed over time at altitude to high altitude can suppress T-cell function (proliferation) as well as alter T-cell subset ratios [ 69 , 70 ]. In a well controlled, multifaceted study now referred to as Operation Everest II, seven male subjects were progressively brought to a simulated altitude of 7,620 m (25,000 ft) in a hypobaric chamber over the course of 4 weeks [ 48 ]. Results indicated that T-cell function was signifi cantly impaired during hypoxia as indicated by signifi cant reductions in both phytohaemagglutinin (PHA)-stimulated lymphocyte proliferation and protein synthesis.…”

Changes in the Levels of Cytokines in Both Diabetic/Non-Diabetic Type I Children Living in a Moderate Altitude Area in Saudi Arabia

“…High altitude exposure influences much immune function (Mazzeo et al, 1994;, including mobilization of T-cells and NK cells, and regulation of cytokine production and release (Klokker et al, 1993;Pedersen and Steensberg, 2002). Regardless of the mechanism, it appears clear that acute exposure to altitude/hypoxia results in alterations of specific components of the immune system (Meehan et al, 1988;Klokker et al, 1993;Mazzeo et al, 1994;Steensberg 2002, Facco et al, 2005). Recently, more attention has been directed toward examining the influence of hypoxia on inflammatory cytokines.…”