Differential effects of hypergravity on immune dysfunctions induced by simulated microgravity

Abstract

Microgravity (μg) is among the major stressors in space causing immune cell dysregulations. These are frequently expressed as increased pro-inflammatory states of monocytes and reduced activation capacities in T cells. Hypergravity (as artificial gravity) has shown to have beneficial effects on the musculoskeletal and cardiovascular system both as a countermeasure option for μgrelated deconditioning and as "gravitational therapy" on Earth. Since the impact of hypergravity on immune cells is sparsely explored, we investigated if an application of "mild" mechanical loading of 2.8 g is able to avoid or treat μgmediated immune dysregulations. For this, T cell and monocyte activation states and cytokine pattern were first analyzed after whole blood antigen incubation in simulated μg (s-μg) by using the principle of fast clinorotation or in hypergravity. Subsequent hypergravity countermeasure approaches were run at three different sequences: one preconditioning setting, where 2.8 g was applied before s-μg exposure and two therapeutic approaches in which 2.8 g was set either intermediately or at the end of s-μg. In single g-grade exposure experiments, monocyte pro-inflammatory state was enhanced in s-μg and reduced in hypergravity, whereas T cells displayed reduced activation when antigen incubation was performed in s-μg. Hypergravity application in all three sequences did not alleviate the increased pro-inflammatory potential of monocytes. However, in T cells the preconditioning approach restored antigen-induced CD69 expression and IFNγ secretion to 1 g control values and beyond. This in vitro study demonstrates a proof of concept that mild hypergravity is a gravitational preconditioning option to avoid adaptive immune cell dysfunctions induced by (s-)μg and that it may act as a booster of immune cell functions.

Monitoring functional immune responses with a cytokine release assay: ISS flight hardware design and experimental protocol for whole blood cultures executed under microgravity conditions

“…We have previously applied this method in a clinical study of immune-compromised patients ( Kaufmann et al, 2013 ; Feuerecker et al, 2018 ) and during winter-over campaigns at Concordia station in Antarctica ( Feuerecker et al, 2019 ). Furthermore, this assay was suitable to measure the effects of simulated microgravity compared to samples incubated at 1 g ( Van Walleghem et al, 2017 ) or hypergravity ( Moser et al, 2023 ) and has been applied to study astronauts pre- and postflight after a long-term space mission to the ISS ( Buchheim et al, 2019 ).…”