Effects of Exercise Interventions in Graft-Versus-Host Disease Models

Abstract

Graft-versus-host-disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is associated with high morbimortality and decreased patients' physical capacity. We evaluated the effects of an 11-week moderate-intensity exercise (treadmill) training program performed after allo-HSCT in a murine acute (aGVHD) and chronic GVHD model (cGVHD). Female mice (aged 8-12 weeks) were randomly assigned to the exercise or the control group. They completed a maximal treadmill test before allo-HSCT (with donor bone marrow cells and splenocytes) and after the 11-week period, during which we evaluated clinical severity scores and survival (Kaplan-Meier method). Before allo-HSCT and at days +21, +52 and +83 (upon sacrifice), we collected blood samples for immune cell reconstitution and cytokine analysis. The main results were that (i) in aGVHD, exercise improved maximal physical capacity over the 11-week period compared with pre-allo-HSCT conditions (p < 0.001 for the between-group comparison) and benefited total clinical score evolution (p = 0.05 for the group × time interaction effect), without altering immune reconstitution; (ii) in cGVHD, exercise training resulted in a lesser deterioration of physical capacity after 11 weeks (p = 0.023). Our results highlight the potential beneficial effects of exercise as coadjuvant intervention against GVHD, especially in the acute form of the disease.