Effects of a training program on the autonomic nervous system and innate immune response in autoimmune disease/spondyloarthritis   July 8th, 2021

Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Research by Kox M. et al. (1,2) evaluated the effects of a training program on the autonomic nervous system (ANS) and innate immune response. However, both the ANS and innate immune system are regarded as systems that cannot be voluntarily influenced. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 days in meditation (third eye meditation), breathing techniques (i.e., cyclic hyperventilation followed by breath retention), and exposure to cold (i.e., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. Also in the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms, such as fever, nausea, headache, and shivering were lower in the intervention group. In conclusion, they demonstrated that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. The fact that people trained in the Wim Hof Method (WHM) could voluntarily influence their immune system was remarkable.

These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases. As the study found increased levels of anti-inflammatory markers, researchers started to wonder whether this was only the case for healthy individuals during acute inflammation, or whether the method could potentially be used for patients suffering from chronic inflammation-related conditions. This was precisely what the study of Buijze G.A. et al. investigated. The goal was to assess whether the WHM could modulate innate immune responses in patients with axial spondyloarthritis (axSpA), which is a chronic rheumatic inflammation of the spine. They primarily wanted to know whether the WHM could safely be applied in this group of patients. Further, they also looked for changes in inflammatory markers that are valid biomarkers to test disease activity in patients. During the study, they made use of patient-reported questionnaires on disease activity and quality of life. So, what did they actually do? Twenty-four patients with axSpA were randomly divided into a treatment and control group. The treatment group received extensive training in the WHM over a period of 8 weeks, both during the group training and at home. During those 8 weeks, measurements in terms of levels of inflammatory markers and the questionnaires were taken. The study showed positive results, the WHM was found to be safe to practice for patients with axSpA, as no safety signals occurred during the intervention. Secondly, a decrease in inflammatory markers was found for those trained with the WHM as compared to the control group. A significant decrease in erythrocyte sedimentation rate levels was shown, as well as a decrease in serum calprotectin levels, although the latter did not reach statistical significance. What do these decreases mean? It indicates that the disease activity declines – the lower the inflammatory levels, the less sick a patient with axSpA is. Finally, various self-reported patient measures of disease activity and quality of life improved following the intervention.

To conclude, this study is a promising discovery of the effect of the WHM for patients with immune-mediated inflammatory conditions. It is not only the first study to test the effects of the WHM in patients rather than healthy individuals, but it also shows positive effects on safety, anti-inflammatory markers, and self-reported mental and physical health. This could possibly have major implications in treatment protocols for people with chronic inflammatory conditions and could serve as a basis for further research.

Luc Vanderweeen

Master of Science in Spinal Manual Therapy and Physiotherapy
Rug-Schouder-Nekcentrum, Schepdaal, Belgium
Pain in Motion international research group

2021 Pain in Motion

References and further reading:

Buijze GA, De Jong HMY, Kox M, van de Sande MG, Van Schaardenburg D, Van Vugt RM, et al. (2019) An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis – A proof of concept trial. PLoS ONE 14(12): e0225749. https://doi.org/ 10.1371/journal.pone.0225749

Kox M, Stoffels M, Smeekens SP, van Alfen N, Gomes M, Eijsvogels TMH, et al. The influence of con- centration/meditation on autonomic nervous system activity and the innate immune response: a case study. Psychosom Med. 2012; 74(5):489–94. https://doi.org/10.1097/PSY.0b013e3182583c6d

Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FCGJ, van der Hoeven JG, et al. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A. 2014; 111(20):7379–84. https://doi.org/10.1073/pnas.1322174111