Chronic hypoxia stimulates an enhanced response to immune challenge without evidence of an energetic tradeoff

Abstract

There is broad interest in whether there is a tradeoff between energy metabolism and immune function, and how stress affects immune function. Under hypoxic stress, maximal aerobic metabolism is limited, and other aspects of energy metabolism of animals may be altered as well. Although acute hypoxia appears to enhance certain immune responses, the effects of chronic hypoxia on immune function are largely unstudied. We tested: (1) whether chronic hypoxia affects immune function and (2) whether hypoxia affects the metabolic cost of immune function. First, flow cytometry was used to monitor the peripheral blood immunophenotype of mice over the course of 36 days of hypoxic exposure. Second, hypoxic and normoxic mice were subjected to an adaptive immune challenge via keyhole limpet hemocyanin (KLH) or to an innate immune challenge via lipopolysaccharide (LPS). The resting metabolic rates of mice in all immune challenge treatments were also measured. Although hypoxia had little effect on the peripheral blood immunophenotype, hypoxic mice challenged with KLH or LPS had enhanced immunological responses in the form of higher antibody titers or increased TNF-α production, respectively. Initially, mice exposed to hypoxia had lower metabolic rates, but this response was transitory and resting metabolic rates were normal by the end of the experiment. There was no effect of either immune challenge on resting metabolic rate, suggesting that mounting either the acute phase response or a humoral response is not as energetically expensive as previously thought. In addition, our results suggest that immune responses to chronic and acute hypoxia are concordant. Both forms of hypoxia appear to stimulate both innate and adaptive immune responses.