Immune Modulating Chronic Fatigue Syndrome Trial Indicates Changes Occurring

Discussion in 'ME/CFS and FM News' started by Cort, Oct 23, 2015.

  1. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Immune Modulators To the Fore in Chronic Fatigue Syndrome

    "The results of this study may expand treatment options for patients with CFS, for whom graded exercise therapy and cognitive behavioral therapy are the only evidence-based interventions that exist at this moment."


    The Rituximab trials, Ampligen studies, the etanercept work by Fluge and Mella, and statements by Dr. Klimas indicate that researchers are becoming more comfortable with the idea of using powerful immune modulators to treat chronic fatigue syndrome.

    Within the past year an ME/CFS immune modulator clinical trial has begun in a country - the Netherlands - best known for its CBT studies. If the trial is successful it will open up new treatment possibilities for ME/CFS.

    It's also an example of changes that appear to be slowly occurring. Somebody, after all, got enough money together to do what an appears to be a quite expensive trial on an immune modulator in the Netherlands. That's something to think about.


    Anakinra is an IL-1 receptor antagonist; i.e. it stops IL-1 -a key pro-inflammatory cytokine that broadly regulates the immune response during infection - from working. Different types of IL-1 prompt the hypothalamus to produce fever, rush immune cells to the site of infection, lower blood pressure and increase pain sensitivity.

    Eleven members of the ILI-1 family are produced mostly by immune cells associated with the innate or early immune response such as macrophages, monocytes, fibroblasts, and dendritic cells. When cells are stressed by low oxygen levels, oxidative stress, infection, high acid levels, etc. they also put out precursors to IL-1a called alarmins that alert the immune system to the possibility that danger may be present.

    IL-1 also plays a major role in neuroinfllammation. A recent review concluded that neuroinflammation (microglial activation) in animal studies is associated with increased IL-1b, TNF-a and several toll-like receptors.

    IL-1 antagonists are used to treat rheumatoid arthritis and other autoinflammatory syndromes as well as gout, epilepsy and inflammatory lung diseases. According to Wikipedia, blocking IL-1 production is now considered standard therapy in the treatment of autoimmune disorders and cancer.

    Cytokine Blockers in Chronic Fatigue Syndrome?

    Cytokine blockers have been mostly blocked from being used in ME/CFS in part because cytokine results in ME/CFS tend to be very variable. Neither IL-1 nor any other cytokine has being definitively associated with it.

    Some successes have occurred. The Lipkin/Hornig cytokine study showed cytokine elevations early in the disease, and Taylor was able to produce an algorithm involving Il-6, IL-8, IL-23 and I-1a and other cytokines that correctly identified 80% of post-infectious mononucleosis patients with chronic fatigue.

    Broderick's and Younger's work, however, suggests that cytokine levels may not need to be high to have significant effects. The altered immune networks Broderick has found in chronic fatigue syndrome indicate that given the right context, small cytokine elevations can have major impacts on the rest of the immune system.

    A further complication involves relating cytokine levels in the blood to immune activity in the brain. The Anakinra sudy authors report that concentrations of cytokines in the blood rarely reflect what is happening in the brain. They propose, therefore, that the only way to accurately assess a cytokine's contributions to a disease is block them using drugs and see what happens. That's what is happening here.

    Anakinra, they noted, is a good cytokine inhibitor to try out in ME/CFS because it does not cause severe side effects.

    Given their reasoning it's possible that emerging evidence of neuroinflammation in ME/CFS helped get this study underway. It also suggests that more definitive evidence of neuroinflammation in ME/CFS and FM - if it occurs- should greatly open the possibilities for treatments and more clinical trials.

    This randomized, placebo-controlled trial will measure symptom levels, functionality, pain levels, psychological distress, cytokine levels, cortisol and and even the microbiome (gut flora).

    It's not clear who is funding what appears to be a rather expensive study. (The responsible party is listed as Radboud University).

    The study has already begun and is expected to last through June, 2016. The contact person for the study is Megan Roerink, MD at'

    Attitudes Slowly Shifting

    This study is another indication that attitudes are slowly but hopefully surely changing - and that the treatment possibilities for ME/CFS are expanding in places one might not think they would. Just recently we saw a UK university, hospital and two trusts herald their new alliance by referring to work they did on muscle problems in ME/CFS. Fluge and Mella have been given enough room to experiment not just with Rituximab but with other immune modulators in Norway. It was jarring but hopeful to see Simon Wessely of all people suggest it was time for an officially sanctioned UK Rituximab trial.

    Despite its history of immune research, the U.S. continues to be the odd man out. The NIH is a major funder of drug trials yet Ampligen was treated harshly by the FDA panel and has, despite its promise and the needs of the ME/CFS community, received no federal help. Rituximab has had solid results in small trials as well, but as yet no help from the federal government in producing a U.S. clinical trial has occurred.

    When the biggest medical research agency in the world will step up and help out is a very good question. For now, it's good to see other countries taking the lead on new treatment possibilities in ME/CFS.
    Last edited: Nov 23, 2015
    Seanko, kmdenmark, Tami and 3 others like this.
  2. Alexa

    Alexa New Member

    Hi Cort

    Thanks for this, as for everything you do.

    I have sometimes used an antgroposophical immune modulator, Iscador, viscum album, derived from mistletoe. I took it initially for breast cancer in 1992 and later for chronic fatigue sundrome, with varying results..

    I have a supply and will trial it again when my situation is stable enough that the outcomes are clear.

    Literature is hard to track down as much research is in German.

    Have you come across ut?

    Best wishes

  3. Alexa

    Alexa New Member


    Struggling with the forum page reply! It went before ready, inckuding typos. It is anthroposophical immune modulator, Iscador.

    These may be useful:

    Original Article
    Anthroposophic Medicine: An Integrative Medical System
    Originating in Europe
    Medicina antroposófica: un sistema de medicina integradora que tiene su
    origen en Europa
    Gunver S. Kienle, Dr med, Germany; Hans-Ulrich Albonico, Dr med, PhD, Switzerland; Erik Baars, Dr med, MSc, PhD,
    The Netherlands; Harald J. Hamre, Dr med, Germany, Norway; Peter Zimmermann, Dr med, PhD, Finland; Helmut
    Kiene, Dr med, Germany

    Büssing A. Immune modulation using mistletoe extracts. Influencing cell function through subcutaneous and intravenous application. Arzneim -Forsch /Drug Res 2006; 56(6a):508-515.

    Elluru S, Van Huyen JP, Delignat S, Prost F, Bayry J, Kazatchkine MD et al. Molecular mechanisms underlying the immunomodulatory effects of mistletoe (Viscum album L.) extracts Iscador. Arzneimittelforschung 2006; 56(6A):461-466.
  4. Alexa

    Alexa New Member


    Finally, this one.


    Journal of Clinical Immunology, Vol. 26, No. 4, July 2006 (C 2006)
    DOI: 10.1007/s10875-006-9023-5
    Immunologic Effector Mechanisms of a Standardized Mistletoe
    Extract on the Function of Human Monocytes and Lymphocytes
    in vitro, ex vivo, and in vivo
  5. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Thanks Alexa.

    I have never heard of it but I'm glad to hear of yet another possibility...The more science looks the more possbilities, it seems, there are. :)
  6. Ros

    Ros New Member

    Perhaps I am just being cynical, but I can't help feeling that using a (largely subjective) fatigue scale as the primary outcome measure is less than ideal. Even taking the secondary measures into account, the effects of the drug would have to be pretty dramatic in terms of 'sickness impact' and 'physical and social functioning' to show up in just 4 weeks in a condition that can fluctuate hugely simply as a result of changes in daily activity. How does one differentiate one effect from the other?

    I long to see more trials that look at cytokine levels and physical functioning 24-48 hours after an 'exercise challenge' - said 'exercise challenge' to be completed both before a drug intervention and after it. That way, we would be looking at possible changes in what most people with ME/CFS consider to be a cardinal symptom of the condition. So the question I'd want to be asking in a study like this is, 'Does anakinra reduce that effect?' - a question the study isn't really designed to answer.

    It will be good if they find that anakinra does do something. However, it being a Dutch study, the cynical side of me is wondering whether a negative result will be used against us, limiting further research in this area rather than encouraging it?
  7. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    The Netherlands is a strange place indeed for this study to show up. I wonder who is funding it?

    You would have to have a strong effect show up for the study to work. I wonder about the heterogeneity in this population - as in every study. There was no way to subset the patients apparently.

    An exercise challenge would give a lot of information for sure. That would be most interesting.