Fitness Shifts the Balance from Inflammation to Repair among People with Progressive MS

[ActiveMSers]

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

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

Author to whom correspondence should be addressed.
Academic Editors: Lorena Perrone, Carola Yvette Förster and Michiaki Nagai
Biomolecules 2021, 11(4), 504; https://doi.org/10.3390/biom11040504
Received: 5 March 2021 / Revised: 20 March 2021 / Accepted: 24 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Metabolic and Neurotrophic Pathways Driving the Brain-Heart-Axis)

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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 (V⋅O2max). People with MS achieved about 50% lower V⋅O2max (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 V⋅O2max 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.

Conclusions

People with progressive MS using walking aids achieved about 50% lower V⋅O2max than controls. At rest, there were no significant differences in BDNF between MS and controls, however, IL-6 was significantly higher in MS. In the MS group, greater ability to upregulate BDNF during maximal exercise was strongly associated with faster walking speed and higher fatigue. Higher V⋅O2max was strongly associated with a shift in BDNF/IL-6 ratio from inflammation to repair when considering both groups together. We present evidence that fitness and exercise indicate a shift in the balance of blood biomarkers towards a repair phenotype even among people who have accumulated significant MS-related disability. How exercise-induced BDNF may influence the neuro-immune axis and interact with the blood-brain barrier is an important area of future research.

FULL ARTICLE:
https://www.mdpi.com/2218-273X/11/4/504

[ActiveMSers]

The entire study is available not only to read for free, but also to share for free with attribution under the Creative Commons license.

[ActiveMSers]

Researchers in every MS exercise study always opine "more research is needed." At what point will they say, Just exercise already, dammit? While reading this paper is a heavy lift, something clearly beneficial is going on in our brains when we workout. There's a reason neurologists are starting to prescribe exercise. 'Bout time.

[Suebee]

Thanks Dave, I’m always looking for evidence based activities I can try to Improve my fitness. The article is dense but I think this excerpt is article in nutshell, “ 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]. While IL-6 is pro-inflammatory and linked to neurodegeneration, the neurotrophin brain-derived neurotrophic factor (BDNF), produced by both glial cells and contracting muscle, regulates synaptic change and use-dependent brain plasticity [10]. Aerobic exercise, by upregulating neurotrophins [11,12,13] and altering cytokine levels [14,15,16,17], could be neuroprotective in MS, thereby facilitating neuroplasticity and protecting against functional decline [11,13,18].” In short, exercise is good. It looks like this study used walking pace to achieve aerobic level, but it references interesting study on aerobic fitness using several progressive exercise moves for stroke survivors... https://www.frontiersin.org/articles/10.3389/fphys.2017.00809/full?report=reader it used I ntermittent functional training (IFT). It was described “The IFT protocol lasted 30 min and involved performing impairment specific multi-joint task-oriented movements structured into circuits lasting ~3 min and allowing 30–45 s recovery between circuits. The aim was to achieve an average heart rate (HR) 30-50 beats above resting without using traditional ergometer-based aerobic exercise.”
and it has illustration of different exercises used to increase aerobic fitness ..https://www.frontiersin.org/files/Articles/298187/fphys-08-00809-HTML/image_m/fphys-08-00809-g001.jpg. Like other study, it says more research is needed .....