Fitness Shifts the Balance of BDNF and IL-6 from Inflammation to Repair among People with Progressive Multiple Sclerosis.

Augustine Joshua Devasahayam,Liam Patrick Kelly,Craig Stephen Moore,John Bradley Williams,Michelle Ploughman

doi:10.3390/biom11040504

Augustine Joshua Devasahayam, Liam Patrick Kelly + Show 3 more

Open Access

https://doi.org/10.3390/biom11040504

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Journal: Biomolecules	Publication Date: Mar 26, 2021
Citations: 15	License type: CC BY 4.0

Affiliation: Memorial University of Newfoundland

Abstract

Physical sedentarism is linked to elevated levels of circulating cytokines, whereas exercise upregulates growth-promoting proteins such as brain-derived neurotrophic factor (BDNF). The shift towards a ‘repair’ phenotype could protect against neurodegeneration, especially in diseases such as multiple sclerosis (MS). We investigated whether having higher fitness or participating in an acute bout of maximal exercise would shift the balance of BDNF and interleukin-6 (IL-6) in serum samples of people with progressive MS (n = 14), compared to matched controls (n = 8). Participants performed a maximal graded exercise test on a recumbent stepper, and blood samples were collected at rest and after the test. We assessed walking speed, fatigue, and maximal oxygen consumption (). People with MS achieved about 50% lower (p = 0.003) than controls. At rest, there were no differences in BDNF between MS and controls; however, IL-6 was significantly higher in MS. Higher was associated with a shift in BDNF/IL-6 ratio from inflammation to repair (R = 0.7, p = 0.001) when considering both groups together. In the MS group, greater ability to upregulate BDNF was associated with faster walking speed and lower vitality. We present evidence that higher fitness indicates a shift in the balance of blood biomarkers towards a repair phenotype in progressive MS.

Highlights

Published: 26 March 2021Globally, more than 2.3 million people live with multiple sclerosis (MS), and of those, over one million people have a progressive form of MS, a type with fewer inflammatory relapses but more prominent neurodegeneration [1]
We found that a higher brain-derived neurotrophic factor (BDNF)/IL-6 ratio was associated with faster walking speed, lower fatigue, and higher fitness when considering MS and controls together
People with progressive MS using walking aids achieved about 50% lower VO2max than controls

Summary

Introduction

Published: 26 March 2021Globally, more than 2.3 million people live with multiple sclerosis (MS), and of those, over one million people have a progressive form of MS, a type with fewer inflammatory relapses but more prominent neurodegeneration [1]. Why some people remain stable and others progress is not clear, and experts in the field have prioritised research to accelerate the development of effective therapies for people with progressive MS [2,3,4] One of these efforts is to create novel rehabilitation strategies that combine the reparative, neuroplastic, cardiorespiratory, and metabolic benefits of aerobic exercise in order to promote brain repair [5]. A recent study reported that heightened levels of IL-6 in cerebrospinal fluid were associated with blunted capacity for neuroplasticity in 150 people with MS [7]. These inflammatory cytokines are toxic to the brain [8] but can be inhibited by participation in physical exercise [9].

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