{"id":15438,"date":"2018-02-02T10:37:33","date_gmt":"2018-02-02T10:37:33","guid":{"rendered":"http:\/\/wames.org.uk\/cms-english\/?p=15438"},"modified":"2018-02-02T10:38:25","modified_gmt":"2018-02-02T10:38:25","slug":"neid-disease-study-suggests-neuro-endocrine-immune-systems-work-together-to-produce-me-cfs","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/neid-disease-study-suggests-neuro-endocrine-immune-systems-work-together-to-produce-me-cfs\/","title":{"rendered":"NEID disease? Study suggests neuro, endocrine & immune systems work together to produce ME\/CFS"},"content":{"rendered":"

Simmaron Research<\/strong> blog post, by Cort Johnson, 26 January 2018: NEID Disease? Study Suggests Neuro, Endocrine and Immune Systems Work Together to Produce ME\/CFS<\/a><\/h3>\n

 <\/p>\n

Bruun Wyller continues to surprise. When last heard from this erstwhile cognitive behavioral therapy (CBT) proponent asserted that more research into Epstein-Barr virus in chronic fatigue syndrome (ME\/CFS) was needed. Now he\u2019s looking at the interaction between the immune and endocrine systems.<\/p>\n

The Evolution of a Chronic Fatigue Syndrome (ME\/CFS) Researcher? CBT Proponent Calls for More Herpesvirus Research<\/a><\/p>\n

Transforming growth factor beta (TGF-\u03b2) in adolescent chronic fatigue syndrome<\/a> Vegard Bruun Wyller, Chinh Bkrong Nguyen, Judith Anita Ludviksen and Tom Eirik Mollnes.\u00a0 J Transl Med (2017) 15:245<\/p>\n

Wyller begins his new study reporting that systemic inflammation is probably present and B-cell functioning is impaired (if modestly) in ME\/CFS, but that the picture regarding cytokines is muddier. A meta-analysis of 38 ME\/CFS cytokine studies examining 77 cytokines found only one standout \u2013 a cytokine called TGF-B. It was consistently elevated in 2\/3rds of the studies.<\/p>\n

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Wyller suggests an unusual neuroimmune connection involving TGF-beta and stress hormones such as cortisol (pictured) may be present<\/p><\/div>\n

Given its unusual and consistent appearance in cytokine study results, why TGF-B has gotten so little attention in ME\/CFS is unclear. The fact that it\u2019s kind of a weird cytokine probably doesn\u2019t help. Secreted by macrophages and some other immune cells, TGF-B can function as both an anti and pro-inflammatory cytokine depending on the situation it\u2019s in.<\/p>\n

It\u2019s three forms are involved in a multitude of regulatory processes involving inflammation and immunity.\u00a0 It does more than participate in the immune system; TGF-B also affects or is affected by the two stress response systems in our bodies \u2013 the HPA axis and autonomic nervous system. All that makes TGF-B a complex character indeed.<\/p>\n

Take our two stress response systems. During stressful situations increased TGF-B levels<\/a> appear to be associated with increased levels of cortisol \u2013 the main stress hormone of the HPA axis.\u00a0 An ME\/CFS study examining the gene expression of immune cells found an abnormally high expression of genes that interact with the HPA axis and autonomic nervous system. That suggested that a significant immune-hormone component is present. Indeed, ME\/CFS has long been characterized as a neuroendocrineimmune (NEID) \u2013 a disease that effects all three systems.<\/p>\n

In this study Wyller, a Norwegian researcher, again used his own broad definition of ME\/CFS to find patients, but this time he did post hoc analyses using the Fukuda and Canadian Consensus criteria to determine if different definitions of ME\/CFS made a difference \u2013 they didn\u2019t). As always, Wyller studied adolescents \u2013 a lot of them (n=120) and 68 controls to produce a very nice sized study. The data analysis took a long time; the data itself was collected from 2010-2012.<\/p>\n

TGF-B actually comes in three forms ((TGF\u2011\u03b21, TGF\u2011\u03b22 and TGF\u2011\u03b23). For the first time ever in ME\/CFS Wyller tested for all three forms of TGF-B, as well as norepinephrine, epinephrine and cortisol (urine) and c-reactive protein (serum).\u00a0\u00a0 He also assessed heart rate variability, and in 29 patients examined their whole blood gene expression. \u00a0Questionnaires assessing fatigue, inflammatory symptoms, post-exertional malaise, sleep, mood and anxiety were also given.<\/p>\n

Results<\/strong>
\nWyller expected TGF-B levels to be higher in his adolescent ME\/CFS patients, but to his surprise even using the CCC and Fukuda criterias, they were not. Nor was TGF-B associated with any clinical markers such as fatigue, PEM, sleep problems, etc.<\/p>\n

Wyller suggests an unusual neuroimmune connection involving TGF-beta and stress hormones such as cortisol (pictured) may be present
\nThe study was looking like a bust until Wyller dug a little deeper. It turned out that TGF-B levels were associated with increased levels of the stress hormones cortisol, norepinephrine and epinephrine in the ME\/CFS patients but not in the healthy controls.<\/p>\n

An unusual immune-endocrine interaction was occurring in ME\/CFS patients that was not found in the healthy controls. For some reason, TGF-B\u00a0 levels rose in conjuction with stress hormones in the ME\/CFS patients but not in the healthy controls.\u00a0 All three TGF-B isoform displayed this association.<\/p>\n

Plus that association also correlated with symptom severity. Wyller found that the TGF-B-cortisol-autonomic nervous system correlation was strongest in the most fatigued ME\/CFS patients.\u00a0 Less fatigued ME\/CFS patients, on the other hand, had much less of this association.<\/p>\n

Once again, context appeared to be king in the ME\/CFS patients. The levels of TGF-B didn\u2019t matter but the network they were embedded in did. A similar scenario showed up in the huge cytokine study conducted by Dr. Montoya and Mark Davis of Stanford. That study, like Wyller\u2019s, didn\u2019t find high levels of cytokines, but it did find that even normal cytokine levels affected symptoms. That suggested some sort of immune hypersensitivity, perhaps associated with some unusual network functioning, was present.<\/p>\n

Now Wyller apparently finds an immune and autonomic nervous sensitivity to TGF-B. It\u2019s not the cytokine levels themselves but the effect they have on stress hormones.\u00a0 Indeed, Wyller suggested that the primary disease mechanism in ME\/CFS is not altered immune production but altered immune control. Somehow the immune system is affecting other systems in unusual ways.<\/p>\n

That\u2019s an intriguing idea given what we\u2019ll shortly see from Dr. Klimas, whose intense testing during exercise suggests that exercise induced immune activity trips off autonomic nervous system problems in ME\/CFS. Gordon Broderick\u2019s network studies suggest that cytokine levels don\u2019t need to be high to have untoward effects on ME\/CFS patients \u2013 they simply have to be embedded in an unusual immune network.<\/p>\n

Wyller believes a complex neuro-endocrine-immune interaction may be contributing to the fatigue and possibly the EBV issues in ME\/CFS.
\nDr. Klimas will be trying in a series of small studies to move those systems back to normal this year. (More on that later.)<\/p>\n

Wyller\u2019s findings suggest that his \u201csustained arousal\u201d hypothesis may be correct and that the \u201csustained arousal\u201d he believes is present in ME\/CFS is being triggered by the immune system. His small gene expression study possibly bares this out. Wyller warned about reading too much into the gene expression analysis because of the small sample size (n=29). The analysis found, though, that the TGF-B3 isoform was negatively associated with reduced expression of two B-cell genes (TNFRSF13C and CXCR5).<\/p>\n

Wyller suggested that TGF-B3 may be altering the effect that cortisol \u2013 the master immune regulator \u2013 has on B-cell genes in ME\/CFS.\u00a0 If TGF-B and cortisol combine to smack B-cell genes in ME\/CFS, Wyller suggests that could translate into problems reining in Epstein-Barr virus (EBV) \u2013 a common trigger in ME\/CFS.\u00a0 Wyller\u2019s earlier gene expression study, in fact, suggested that B-cell problems could be the key to the EBV problems seen in ME\/CFS. Now Wyller suggests that these B-cell problems could result from a complex interaction between TGF-B and cortisol.<\/p>\n

Wyller\u2019s going to check out that interaction in a study which will determine how effectively the B-cells in ME\/CFS patients respond to EBV in the presence of neuroendocrine hormones. If cortisol or other neuroendocrine hormones impair the ability of B-cells to whack EBV in ME\/CFS, Wyller may have uncovered one reason why mononucleosis is such a common trigger for ME\/CFS.<\/p>\n

Mold Connection?<\/strong>
\nWyller\u2019s focus on the research literature apparently precluded him from exploring another TGF-B angle. Mold has become a hot if little studied topic in ME\/CFS. For over a decade, mold doctor Ritchie Shoemaker has asserted that elevated TGF-B levels play a major role<\/a> in mold related illnesses.\u00a0 Instead of B-cells, though, Shoemaker ties TGF-B issues to T cell problems and reduced blood flow in the capillaries, which translate into reduced oxygen uptake and problems with producing energy in the mitochondria \u2013 a key theme in ME\/CFS.<\/p>\n

Shoemaker, interestingly, asserts those blood flow and immune problems mirror what is happening in sepsis. In fact, Shoemaker believes that the chronic inflammatory response syndrome (CIRS) he sees in his patients is a chronic form of sepsis. Over ten years ago ME\/CFS specialist Dr. David Bell proposed a chronic form of sepsis exists<\/a> in ME\/CFS as well.<\/p>\n

Read about the future research of Simmaron Research<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simmaron Research blog post, by Cort Johnson, 26 January 2018: NEID Disease? Study Suggests Neuro, Endocrine and Immune Systems Work Together to Produce ME\/CFS   Bruun Wyller continues to surprise. When last heard from this erstwhile cognitive behavioral therapy (CBT) … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[618,729,221,224,2328,1901,1902,3991],"class_list":["post-15438","post","type-post","status-publish","format-standard","hentry","category-news","tag-cort-johnson","tag-cortisol","tag-ebv","tag-epstein-barr-virus","tag-simmaron-research","tag-tgf-","tag-transforming-growth-factor-beta","tag-vegard-bruun-wyller"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-410","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/15438","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=15438"}],"version-history":[{"count":3,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/15438\/revisions"}],"predecessor-version":[{"id":15444,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/15438\/revisions\/15444"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=15438"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=15438"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=15438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}