Polyethylene glycol but not mifepristone prevents intestinal lymphocyte loss following treadmill exercise in mice

Circulating lymphocyte numbers decrease following intense physical activity, possibly due to exercise-induced apoptosis. Increased reactive oxygen species (ROS) and glucocorticoids (GC) following exercise contribute to lymphocyte apoptosis. Intestinal lymphocyte (IL) numbers also decrease following exercise. Aim: The purpose of this study was to determine the contribution of GC to exercise-induced IL loss. Methods: Female C57BL/6 mice (n = 178) were randomized to five drug conditions: (1) single injection of the glucocorticoid receptor antagonist mifepristone (MIF) solubilized in polyethylene glycol (PEG); (2) three injections of MIF (repeated MIF) PEG; (3) single injection of PEG (PEG); (4) three injections of PEG (repeated PEG); or (5) repeated injections of saline (SAL). Within each drug group mice were further randomized to exercise conditions: (1) control condition (non-exercised); (2) treadmill running with sacrifice immediately following the exercise; or (3) treadmill running with sacrifice 24 h after completion of the exercise. Results: There was a significant exercise effect, across all T lymphocyte subsets, in SAL (P < 0.01), PEG (P < 0.01) and MIF (P < 0.01) treated mice but not in mice given repeated PEG or repeated MIF exposure. The exercise effect was due to reduced IL numbers 24 h post-exercise compared with non-exercised controls. Conclusion: These results suggest that GC are not directly responsible for IL cell loss following exercise. Repeated exposure to PEG may confer protection in the gastrointestinal tract from exercise-induced lymphocyte depletion. Because PEG inhibits ROS generation in experimental cell injury, the mechanisms for IL loss after exercise may involve oxidative stress.