High-intensity interval training attenuates development of autoimmune encephalomyelitis solely by systemic immunomodulation.

The impact of high-intensity interval training (HIIT) on the central nervous system (CNS) in autoimmune neuroinflammation is not known. The aim of this study was to determine the direct effects of HIIT on the CNS and development of experimental autoimmune encephalomyelitis (EAE). Healthy mice were subjected to HIIT by treadmill running and the proteolipid protein (PLP) transfer EAE model was utilized. To examine neuroprotection, PLP-reactive lymph-node cells (LNCs) were transferred to HIIT and sedentary (SED) mice. To examine immunomodulation, PLP-reactive LNCs from HIIT and SED donor mice were transferred to naïve recipients and analyzed in vitro. HIIT in recipient mice did not affect the development of EAE following exposure to PLP-reactive LNCs. HIIT mice exhibited enhanced migration of systemic autoimmune cells into the CNS and increased demyelination. In contrast, EAE severity in recipient mice injected with PLP-reactive LNCs from HIIT donor mice was significantly diminished. The latter positive effect was associated with decreased migration of autoimmune cells into the CNS and inhibition of very late antigen (VLA)-4 expression in LNCs. Thus, the beneficial effect of HIIT on EAE development is attributed solely to systemic immunomodulatory effects, likely because of systemic inhibition of autoreactive cell migration and reduced VLA-4 integrin expression.

Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis.

BACKGROUND: The mechanisms by which exercise training (ET) elicits beneficial effects on the systemic immune system and the central nervous system (CNS) in autoimmune neuroinflammation are not fully understood. OBJECTIVES: To investigate (1) the systemic effects of high-intensity continuous training (HICT) on the migratory potential of autoimmune cells; (2) the direct effects of HICT on blood-brain-barrier (BBB) properties. METHODS: Healthy mice were subjected to high-intensity continuous training (HICT) by treadmill running. The proteolipid protein (PLP) transfer EAE model was utilized to examine the immunomodulatory effects of training, where PLP-reactive lymph-node cells (LNCs) from HICT and sedentary donor mice were analyzed in vitro and transferred to naïve recipients that developed EAE. To examine neuroprotection, encephalitogenic LNCs from donor mice were transferred into HICT or sedentary recipient mice and the BBB was analyzed. RESULTS: Transfer of PLP-reactive LNCs obtained from HICT donor mice attenuated EAE severity and inflammation in recipient mice. HICT markedly inhibited very late antigen (VLA)-4 and lymphocyte function-associated antigen (LFA)-1 expression in LNCs. Transfer of encephalitogenic LNCs into HICT recipients resulted in milder EAE and attenuated CNS inflammation. HICT reduced BBB permeability and the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in CNS blood vessels. INTERPRETATION: HICT attenuates EAE development by both immunomodulatory and neuroprotective effects. The reduction in destructive CNS inflammation in EAE is attributed to systemic inhibition of autoreactive cell migratory potential, as well as reduction in BBB permeability, which are associated with reduced VLA-4/VCAM-1 and LFA-1/ICAM-1 interactions.