# Exercise as it relates to Disease/The effects of exercise on Multiple Sclerosis

This fact sheet examines how "Combined exercise training reduces IFN-γ and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis".

## What is the background to this research?
### What is Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease affecting the central nervous system. It is characterised by progressive demyelination and neurodegenerative events resulting in severe neurological impairments. Most commonly displayed as deficits in sensation, motor, autonomic and cognitive function. The pathogenesis of MS is thought to be due to both genetic and environmental factors with the clinical course of the disease being highly variable amount patients. The variability of symptoms is largely due to the location of the faulty re-myelination or plaque deposits after myelin depletion.

### Prevalence

* In 2008 an estimated 2.5 million people worldwide had been diagnoses with MS.
* Average age of onset is 30 years old.
* More common in females.
* Most common neurological disorder in young adults.

### The role of inflammation in MS

This research has selected two pro-inflammatory cytokines (IFN-γ, IL-17) and one anti-inflammatory cytokine (IL-4) to study. It is well know that exercise can reduce inflammation in chronic disease patients therefore it has been hypothesized that exercise may be able to do similar in MS patients. The type of exercise performed is thought to have differing effects on pro and anti-inflammatory cytokine in MS patients, therefore this study looks at how these three cytokines respond to combined exercise training.

## Where is the research from?

There were 20 women from Iran and Sina who meet the inclusion criteria and participated in this study. All researches involved were from Iran, based at either the University of Tehran or Tarbiat Modares University. This was the first publication for Zahra Gulzari's, the lead author, however the remaining authors have published multiple papers in the past.

## What kind of research was this?

The study design is a randomized control trial (RCT). This means the participants were randomly assigned to either an intervention or control group. The same measures are taken in each group before and after the intervention so that if a change occurs it is reasonable to assume it is due to the intervention. A RCT is considered level II evidence in the evidence hierarchy, level I being a systematic review. RCT's are generally robust studies that aim to minimize bias through the use of randomisation.

## What did the research involve?

The participants in the intervention group were required to partake in three sessions of exercise per week over the course of 8 weeks. The exercise sessions went for approximately one hour and included a warm-up, stretching, aerobic exercise, resistance training and relaxation. All sessions where supervised by a health professional. Maximal oxygen uptake, strength, balance and flexibility were measured pre and post intervention in both groups, as was the Expanded Disability Status Scale (EDSS). Blood samples were also collected at the beginning and end of the intervention to measure cytokine levels of IFN-y, IL-17 and IL-4.
The methodology had a number of limitations. The sample size was very small raising the question as to whether this is a true representation of the population. Another concern is the validity of the outcome measures used for the strength, balance and flexibility testing as well as the EDSS. This lack in detail on how strength, balance and flexibility were measured, and the EDSS also means it would be difficult to replicate the study. While this was not the main focus of the study further detail would have been beneficial.

## What were the basic results?

Upon completion of the intervention the exercise group had significant improvements in their EDSS as well as significant gains in both strength and balance. All parameters measured at the beginning of the 8-week period remained unchanged for the duration of the trial in the control group. Data from the blood samples showed there were significant decreases in the pro-inflammatory cytokines in the intervention group however no change occurred in the anti-inflammatory cytokines. The control showed no significant change for any of the above cytokines.
The results from this study were clearly stated, however there was no normative data provided for the pro and anti-inflammatory cytokines. While the paper demonstrated that there was a reduction in the pro-inflammatory cytokines, there was no explanation to indicate if these levels were still high. Without this information it was difficult to determine the true benefit of the exercise.

## What conclusions can we take from this research?

A large body of research now supports exercise as having a very positive effect on MS patients. While many studies have focused on either aerobic or resistance training very few have focused on combined exercise. This research showed that combined exercise not only improves strength and balance in patients, it also reduces pro-inflammatory cytokines within the immune system. This means exercise has the potential to slow down the course of MS as it is largely inflammation causing the degeneration.
The results above indicate it would be beneficial to repeat the study on a larger sample size using a more robust methodology in order to determine if the results are unbiased and reproducible. Further studies would also be useful in order to provide new evidence to update the MS exercise protocol.

## Implications of this study

This study showed that combined exercise training is a very practical, achievable and cost effective way to reduce inflammation in MS patients. Potentially all MS patients could participate in this type of program, however depending on the disease stage some patients may require more assistance than others. While safety is a concern if exercising with MS however the benefits outweigh the risks, therefore some level of supervision is recommended.

## Further information/resources

For further information regarding MS please go to:
MS Society Australia
Health Direct - Australia
Development of Evidence-Informed Physical Activity Guidelines for Adults With Multiple Sclerosis

## References

* 1 2 3 4 5 6 7 8 9 10 Golzari Z, Shabkhiz F, Soudi S, Kordi M, Hashemi S. Combined exercise training reduces IFN-γ and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. International Immunopharmacology. 2010;10(11):1415-1419.
* 1 2 3 4 5 Küçükali C, Kürtüncü M, Çoban A, Çebi M, Tüzün E. Epigenetics of Multiple Sclerosis: An Updated Review. Neuromol Med. 2014;17(2):83-96.
* ↑ Carr J, Shepherd R. Neurological Rehabilitation, Optimizing Performance. 2nd ed. Edinburgh, Churchill Livingstone: Elsevier; 2010.
* ↑ Dendrou C, Fugger L, Friese M. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545-558.
* ↑ Hoffmann T, Bennett S, Del Mar C. Evidence-Based Practice Across the Health Professions. London: Elsevier Health Sciences APAC; 2013.
* 1 2 Latimer-Cheung A, Martin Ginis K, Hicks A, Motl R, Pilutti L, Duggan M et al. Development of Evidence-Informed Physical Activity Guidelines for Adults With Multiple Sclerosis. Archives of Physical Medicine and Rehabilitation. 2013;94(9):1829-1836.e7.
* ↑ Dalgas U, Stenager E, Ingemann-Hansen T. Review: Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Multiple Sclerosis. 2008;14(1):35-53.