From PLoSOne, 6 July 2015.
A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice
Yvonne Couch(1), Qin Xie(1), Louise Lundberg(1,2), Trevor Sharp(1), Daniel C. Anthony(1)
1) Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, United Kingdom
2) Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxford OX11 0RQ, United Kingdom
Abstract
It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria.
However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved.
At 24 hours post-injection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT.
However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI.
These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS.
From Anticancer Research, August 2015.
Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.
Inui T(1), Kubo K(2), Kuchiike D(3), Uto Y(4), Nishikata T(5), Sakamoto N(6), Mette M(7).
1) Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan Saisei Mirai Cell Processing Center, Osaka, Japan Inui Immunotherapy Clinic, Osaka, Japan contact@saisei-mirai.or.jp.
2) Saisei Mirai Cell Processing Center, Osaka, Japan.
3) Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan Saisei Mirai Cell Processing Center, Osaka, Japan.
4) Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
5) Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe, Japan.
6) Division of Food and Drug Evaluation Science, Department of Community Medicine and Social Healthcare Science, Graduate School of Medicine, Kobe University, Kobe, Japan.
7Inui Immunotherapy Clinic, Osaka, Japan contact@saisei-mirai.or.jp.
Abstract
BACKGROUND
Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades.
Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy.
RESULTS
Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects.
CONCLUSION
We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases.
Dear Yvonne Couch
The abstract from your recent paper (A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice; PLoSOne, 6 July 2015.) states “It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS)…”
You are clearly unaware that the WHO has never classified M.E. as a ‘psychiatric illness’ and that the Brirish government has repeatedly confirmed its support for that position.
You are clearly out of touch with science in the last couple of decades; I wish I was well enough to find more references for you. However, you may wish to read:
• Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome. Rajeevan MS, Dimulescu I, Murray J, Falkenberg VR, Unger ER. Hum Immunol. 2015, Jun 24th.
• Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Funded by the NIH’S Pathways to Prevention (P2P) program.
• The recent Institute of Medicine (IOM) report; USA
• http://www.investinme.org/IIME-Newslet-1502-02.htm
Thirty to forty yeas ago, MS was described as a form of ‘hysteria’, and stomach ulcers were ascribed to ‘stress’. It is astonishing that the same, ignorant and lazy thinking is now causing M.E. to be referred to as a ‘psychiatric illness’ in spite of the evidence to the contrary.
Your sincerely
John Simpson
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“There is evidence that the patients with this illness (M.E.) experience a level of disability that is equal to that of patients with late-stage AIDS, patients undergoing chemotherapy (and) patients with multiple sclerosis,” Professor Nancy Klimas, University of Miami. It has a terrible effect on every aspect of life, making walking, thinking, and reading/writing (among other things) unbelievably difficult – like reading this!
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“People with CFS are as sick and as functionally impaired as someone with AIDS, with breast cancer, with chronic obstructive pulmonary disease ” Bill Reeves of the CDC
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ME/CFS “…is a relatively common illness. The physical symptoms can be as disabling as… rheumatoid arthritis, congestive heart failure and other chronic condition, placing a substantial burden on people with the condition, their families and carers, and hence on society.”
NICE Guideline 2007
Thank you Soloman for this excellent response.
The idea that the pain is ‘all in the head’ and can be cured with ‘mindfulness’ and brain training that I’ve spoken about previously, I hear is creeping into schools now too.
A book recommended to me recently from the CFS clinic is ‘You can Conquer Pain’. It has more caveats than cooked dinners and the 2 pages at the back of the book are excluding people with FM, Osteo and Myofacial pain. Guess it’s not for us then.
There are other books and web sites that are ok though.
Why do children need it apart from the pressure and stress they have to endure these days.
Looks like the latest trend.
Thanks
Good Grief! ME is not a psychiatric illness!
What an astonishingly erroneous opening paragraph for the PlosOne article at the top. Would be interesting to know who funds their research and/or publication?! Perhaps just one letter on behalf of all of us to both the lead scientist of the study and also to the journal editor who can pass it on to the peer reviewers of the article would suffice. What a professional embarrassment for them after all the years of high quality scientific research into a neurological illness.
Dear Yvonne Couch,
I was interested to read your recent article titled: A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice
You state that:
“It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria.”
Given that The World Health Organisation and NICE currently categorise myalgic encephalomyelitis as a neurological condition, might it not be politic to resist the temptation to define it as a ‘psychiatric illness’ prior to its aetiology being established.
If, in the future, ME is found to be autoimmune or neurological in nature, your disease description will be rendered inaccurate, thereby casting doubt upon your findings, which may be sound.
Best regards
Margot
The mea and other charity groups including meruk are doing a very fine job at trying to breathe life into the prospects of patients with this dreadful illness. its very sad to see that two rather pedestrian articles are the sum total of what came out last week. this is very worrying unless the huge grant-issuing agencies like the MIH in the US, ramp up their expenditure on quality biomedically oriented ME/CFS research, we will still be treading water in another 20 years
The medical profession and grant-issuing agencies have behaved in a shocking manner towards he researchers that are just as eager as us, to find medical solutions to this illness.
Senior academics, with an interest in ME, have their promising research grant applications, turned down again and again, on the spurious grounds that the grant applications lacked merit or even more offensive, that they were poorly drawn up.
Please everyone support the responsible ME charities who comission research and do advocacy work, like the two mentioned above.
Jeremy
Last week I asked if my craft group would do their craft fair for ME please. I was given a most definite “NO – we need something that draws people in!!” There are members who don’t believe it’s a real illness and those who just don’t want to know. However, when my 2 daughters say I shouldn’t ‘go on’ about it (they have ME too), I say ‘I will not apologise for going on about it, when it starts people talking, negative or not”. One day when they complain about me, ‘going on about it’ someone may step in and say, well actually it is a very debilitating disease, because I know people who have it and how it’s devastated their lives.”
Talking spreads news and people love to talk and so it gets around. That’s my take on it. Get people talking about it and curiosity sets in.