Repeated Mifepristone And Polyethylene Glycol Exposure Prevent Intestinal Lymphocyte Loss After Treadmill Exercise In Mice

Abstract

0910 Strenuous physical exercise is associated with lymphocytopenia and compromised immune function. Glucocorticoids (GC) and oxidative stress (ROS) produced by exercise are two factors that may be responsible for this lymphocyte cell loss. Purpose: To determine if the GC receptor antagonist mifepristone (MIF) and polyethylene glycol (PEG), commonly used for MIF solubilization and which inhibits ROS production and repairs membrane damage, prevent exercise-induced intestinal lymphocyte cell loss. Methods: One hundred and fifty-three female C57BL/6 mice were given (i) a single s.c. injection of control solution (vehicle), (ii) a single injection of MIF, (iii) repeated injections of MIF solubilized in PEG, or (iv) repeated injections of PEG. Following injection mice were exposed to 90 min of treadmill exercise (28m·min−1, 2° slope) and sacrificed immediately or 24h after exercise. Control mice were exposed to treadmill noise and vibration without running. Following sacrifice intestinal lymphocytes (IL) were isolated and analysed for T and natural kill (NK) subpopulations using flow cytometry. Plasma corticosterone (CORT) was determined by RIA. Results: Plasma CORT was significantly elevated in repeated MIF, nonexercised mice (mean ± SEM; 126.8 ± 3.9ng·ml−1) compared with vehicle (67.9 ± 2.9ng·ml−1), single MIF (77.1 ± 6.8ng·ml−1) and PEG (61.7 ± 6.6ng·ml−1) injected mice (p < 0.001). After exercise there was a significant decrease in total IL recovered from the bowel as well as in CD3+, CD3γδ+, CD8+, CD4+ subsets in vehicle and single MIF conditions. This exercise-associated cell loss was not observed following repeated MIF and PEG injections. However, repeated MIF and PEG failed to inhibit the exercise-associated loss in NK+ cells isolated from the intestine 24h post-exercise. Conclusion: Postexercise IL, but not NK cells, depletion may be mediated by oxidative stress rather than directly by GC: repeated MIF (solubilized in PEG) and PEG alone attenuated the post-exercise drop in cell numbers whereas vehicle and single MIF were associated with pronounced IL depletion. Further studies are needed to confirm whether oxidative stress is the underlying mechanism for depletion in intestinal lymphocytes 24h after exercise. Research supported by a grant from NSERC Canada (LHG).