Effects of Space Flight Conditions on the Function of the Immune System and Catecholamine Production Simulated in a Rodent Model of Hindlimb Unloading

Abstract

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. Objective: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. Methods: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. Results: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. Conclusion: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections.

Osteopontin: Role in immune regulation and stress responses

“…Both HU and CRS are physical stress models containing a significant psychological component that activates neural transmitters and stress hormones (Aviles et al, 2005;Dhabhar et al, 2000). Until now, the role of OPN in the stress response of immune organs has not been examined.…”

“…The results reported here imply an involvement of macrophages, which share the same lineage with osteoclast, in the remodeling of the lymphoid organs in response to HU stress. OPN has in fact been implicated in both macrophage and osteoclast function (Rittling et al, 1998;Aviles et al, 2005). OPN is produced by both cell types and facilitates their function(s), in part via interactions with CD44.…”

Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production

“…Mice were caged individually and suspended for 3 days by the tail by using a strip of adhesive surgical tape attached to a chain hanging from a pulley. Mice were suspended at a 25°angle to the f loor with only the forelimbs touching the f loor (24,38). Food and water were supplied ad libitum.…”

Enhancement of In Vitro Growth of Pathogenic Bacteria by Norepinephrine: Importance of Inoculum Density and Role of Transferrin

“…Although a great deal of evidence suggests that stress-induced neurohormones play a critical role in the outcome of infections (1,3,4,5,7,21,31), the mechanisms by which these hormones act in the host remain unclear. Studies with human and animal models have indicated that increased levels of stress hormones, including norepinephrine (NE), as well as other catecholamines, alter the immune response and physiology of the host (2). High circulatory levels of these hormones are detected in individuals exposed to a variety of physically and/or mentally stressful situations, including trauma, space flight, and sepsis (13,29,31,32).…”