Exercise intensity-dependent immunomodulatory effects on encephalomyelitis.

Background: Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity-dependent effects of ET on the systemic immune system in EAE remain undefined.

Objective: (1) To compare the systemic immune modulatory effects of moderate versus high-intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression.

Methods: Healthy mice performed moderate or high-intensity treadmill running programs. Proteolipid protein (PLP)-induced transfer EAE was utilized to examine ET effects specifically on the systemic immune system. Lymph node (LN)-T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed, by clinical assessment and histopathological analysis. LN-T cells derived from donor trained versus sedentary PLP-immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real-time PCR. T cell-dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli-induced acute peritonitis were examined.

Results: High-intensity training in healthy donor mice induced significantly greater inhibition than moderate-intensity training on proliferation and generation of encephalitogenic T cells in response to PLP-immunization, and on EAE severity upon their transfer into recipient mice. High-intensity training also inhibited LN-T cell proliferation in response to ovalbumin immunization. E. coli bacterial counts and dissemination were not affected by training.

Interpretation: High-intensity training induces superior effects in preventing autoimmunity in EAE, but does not alter immune responses to E. coli infection.