Effects of exercise interventions in graft-versus-host disease models

Cell Transplant. 2013;22(12):2409-20. doi: 10.3727/096368912X658746. Epub 2012 Oct 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chronic Disease
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation*
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Physical Conditioning, Animal*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Severity of Illness Index
  • Transplantation, Homologous
  • Whole-Body Irradiation

Substances

  • Cytokines
  • Ribosomal Protein S6 Kinases, 70-kDa