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 μg-related 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 μg-mediated 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.
Keywords: T cells; artificial gravity; clinostat; cytokines; hypergravity; microgravity; monocytes; preconditioning.
© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.