Impact of Exercise on Innate Immunity in Multiple Sclerosis Progression and Symptomatology

Abstract

Multiple Sclerosis (MS), an idiopathic progressive immune-mediated neurological disorder of the central nervous system (CNS), is characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. It accounts for functional deterioration and lasting disability among young adults. A body of literature demonstrates that physical activity counteracts fatigue and depression and may improve overall quality of life in MS patients. Furthermore, much data indicates that exercise ameliorates chronic neuroinflammation and its related pathologies by tipping cytokine profiles toward an anti-inflammatory signature. Recent data has focused on the direct impact of exercise training on the innate immune system by targeting toll-like receptors (TLRs), signaling pattern recognition receptors that govern the innate immune response, shedding light on the physiological role of TLRs in health and disease. Indeed, TLRs continue to emerge as players in the neuroinflammatory processes underpinning MS. This review will highlight evidence that physical activity and exercise are potential immunomodulatory therapies, targeting innate signaling mechanism(s) to modulate MS symptom development and progression.

Keywords: Multiple Sclerosis; TLRs; cytokines; exercise; innate immunity; neuroinflammation.

Figure 1

Susceptibility to MS is believed to be caused by the complex interaction between genetic, environmental and immunological factors which triggers an immune attack and the initiation of MS. Physical activity has been shown to target inflammatory and immune genes associated with MS neuropathology, exerting an anti-inflammtory effect. Additionally many common presenting symptoms associated with MS have been shown to be improved in response to physical activity.

Figure 2

TLRs reside on the plasma membrane or intracellularly on endosomes and act via the MyD88 or the TRIF pathway leading to the activation of downstream signaling pathways. TLR activation results in the translocation and transcriptional activation of transcription factors NF-κB and IRF-3, and the production of pro-inflammatory genes and IFN inducible genes, respectively.