Hip
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I doubt that. There are however herbs, drugs and supplements that can inhibit IL-1β release.
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Are Infections Just a Trigger of ME/CFS, or an Ongoing Cause of ME/CFS?
- Thread starter Eeyore
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I doubt that. There are however herbs, drugs and supplements that can inhibit IL-1β release.
Anakinra is a monoclonal antibody that inhibits activation of the IL-1 receptor. It's used in wide variety of illnesses, although RA is probably the FDA approved indication. Right now, there isn't a great ability to predict who will respond well to which particular mab, including rituximab. Blocking IL-1 receptors is broadly immunosuppressive - so it will probably work in ME, although you do not want to do that if there is active infection, as it leaves the individual vulnerable. All of these biologic immunosuppressives are not given when there is active infection, as they allow the infection to get worse, and precipitate potentially life threatening infections, especially viral (e.g. JC virus), that don't occur in healthy people.
Dr. Klimas has been talking about doing trials with Anakinra for years, but has not been able to get the funding - I believe it's well over 20k/yr. Most of the biologics used in RA and other chronic autoimmune / autoinflammatory disorders cost on the order of 20-30k/year - even apremilast, which is a small molecule drug, costs nearly that much (for those that don't know, small molecule means it's not a biologic. i.e. it's not an antibody or soluble receptor, which are much harder to produce and can't be given orally - most drugs you take on a regular basis - anything that's a pill pretty much - is a small molecule drug).
I think Anakinra would probably work about as well as rituximab, but no one really knows yet. Dr. Klimas has reasons for choosing that drug - she obviously believes that IL-1 plays a particularly important role.
Dr. Klimas has been talking about doing trials with Anakinra for years, but has not been able to get the funding - I believe it's well over 20k/yr. Most of the biologics used in RA and other chronic autoimmune / autoinflammatory disorders cost on the order of 20-30k/year - even apremilast, which is a small molecule drug, costs nearly that much (for those that don't know, small molecule means it's not a biologic. i.e. it's not an antibody or soluble receptor, which are much harder to produce and can't be given orally - most drugs you take on a regular basis - anything that's a pill pretty much - is a small molecule drug).
I think Anakinra would probably work about as well as rituximab, but no one really knows yet. Dr. Klimas has reasons for choosing that drug - she obviously believes that IL-1 plays a particularly important role.
Hi @Hip, I don;t have Buhner's book on Lyme with me at the moment so I can't check the details but in that book there are study references on how certain herbal molecules act on different pro-inflammatory cytokines. But you're probably right about receptors vs inhibition.
Three herbs I remember were cast' claw, knotweed and stephania tet. because I used them for some time. These three herbs, but esp. the last one, used to have a very powerful suppressive effect on my symptoms.
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Hip
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@xrunner
If we assume that it is glial cells in the vagus nerve (specifically, the Schwann cells) that are infected with a virus in ME/CFS, then we would need some supplements or drugs that can specifically inhibit IL-1β secretion from these infected glial cells.
I compiled a list of drugs and supplements that can inhibit the release of sickness behavior cytokines from microglia and astrocytes (astrocytes are glial cells): the list can be found here. Below I pasted the relevant part of this list for astrocytes:
You can see that Rehmannia glutinosa and alpha lipoic acid both inhibit IL-1β release from astrocytes. I have in fact tried both of these at high doses, but to no noticeable effect.
The drug anakinra mentioned above works in a different way: this drug is a version of IL-1ra, and IL-1ra is in fact a "decoy" IL-1 receptor, that works to mop up the IL-1β, and so prevents IL-1β from activating the real IL-1β receptor.
One problem I can see with anakinra, and possibly with the supplements detailed above, is that there may be poor penetration into the vagus nerve. In his vagus nerve hypothesis paper, Michael VanElzakker says that antivirals have poor penetration into the peripheral nervous system, and so if ME/CFS does involve a vagus infection, antivirals will have reduced effect, due to this lack of penetration. The same may possibly be true for anakinra.
If we assume that it is glial cells in the vagus nerve (specifically, the Schwann cells) that are infected with a virus in ME/CFS, then we would need some supplements or drugs that can specifically inhibit IL-1β secretion from these infected glial cells.
I compiled a list of drugs and supplements that can inhibit the release of sickness behavior cytokines from microglia and astrocytes (astrocytes are glial cells): the list can be found here. Below I pasted the relevant part of this list for astrocytes:
You can see that Rehmannia glutinosa and alpha lipoic acid both inhibit IL-1β release from astrocytes. I have in fact tried both of these at high doses, but to no noticeable effect.
The drug anakinra mentioned above works in a different way: this drug is a version of IL-1ra, and IL-1ra is in fact a "decoy" IL-1 receptor, that works to mop up the IL-1β, and so prevents IL-1β from activating the real IL-1β receptor.
One problem I can see with anakinra, and possibly with the supplements detailed above, is that there may be poor penetration into the vagus nerve. In his vagus nerve hypothesis paper, Michael VanElzakker says that antivirals have poor penetration into the peripheral nervous system, and so if ME/CFS does involve a vagus infection, antivirals will have reduced effect, due to this lack of penetration. The same may possibly be true for anakinra.
What is the sickness behavior cytokine associated for a disinclination to groom? Or a disinclination to mow the lawn because I know it will result in PEM? Or to concentrate too long for the same reason?
What is the sickness behavior cytokine associated for false illness beliefs or conversion disorders? For that matter, where do both of these fall into the sickness behavior scheme of behavior?
How does the sickness behavior model differentiate between symptoms and perception of symptoms? Where does will and choice fall into this theory? As in, I choose not to write too much because I know it will result in a worsening of my symptom cluster? How does the theory accommodate pain, and my decision to avoid that which causes pain, and the motivation for the latter?
What is the sickness behavior cytokine associated for false illness beliefs or conversion disorders? For that matter, where do both of these fall into the sickness behavior scheme of behavior?
How does the sickness behavior model differentiate between symptoms and perception of symptoms? Where does will and choice fall into this theory? As in, I choose not to write too much because I know it will result in a worsening of my symptom cluster? How does the theory accommodate pain, and my decision to avoid that which causes pain, and the motivation for the latter?
Hip
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Duncan, this discussion on the vagus nerve infection hypothesis is a complex and scientific one. I would suggest that you read some of the science, rather than making silly remarks like that.
Despite the name, sickness behavior isn't behavioral in the usual sense of the word. It's an involuntary and uncontrollable biological reaction to illness.
It's the proper medical term for it, but it's not a good one, since it is rather misleading.
I care little even if it is defined as such. I am always concerned when Science or Medicine or advocates or adversaries embrace terms that lend themselves to misappropriation, and hence, manipulation at patients' expense.
But I will let it go. I did not mean to be a distraction.
But I will let it go. I did not mean to be a distraction.
If you think there is an active viral infection, the LAST thing you want to do is suppress the immune system - you'd want to stimulate it. If the vagus theory were correct (which I highly doubt), immunosuppressive drugs could be fatal. Immunosuppression is particularly dangerous with CNS infection.
Hip
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It is kind of behavioral, in the sense that the mental states induced during sickness behavior will lead to changes in animal behavior, and that is precisely the intention, so to speak. The idea is that these induced states will modulate the animal's behavior in a way that helps the animal overcome the infection (and in a way that helps prevent the infection being spread to other animals).
Modulation of behavior of course can occur as a result of any mental states which are induced in the mind, such as mental states induced by hormones. For example, if you suppress the surge of the hormone oxytocin that occurs during the birth process, a mother will no longer show much maternal bonding towards the newly born animals. So oxytocin controls the maternal bonding behavior. And if you artificially increase levels of the hormone testosterone in middle aged males whose testosterone has naturally declined, then you often notice an increase in motivation appearing, along with increased libido. So in this way, testosterone is a factor that helps control motivational and sexual behavior.
But I don't think these psychological terms are any cause for concern. ME/CFS patients have been trying to say that the cognitive and psychological changes we experience are caused by underlying biological reasons, which is what the theory of sickness behavior implies. This is a far cry from what is Wessely's saying, which is that these cognitive and psychological changes are a result of psychological causes. This latter view, the psychogenic "all in the mind" view, is what ME/CFS patients (including myself) are vehemently against.
I actually found it quite interesting that a reduction of grooming behavior is listed among the sickness behavior symptoms, because this is exactly what I noticed in myself, since developing ME/CFS. I used to be a real stickler for things like brushing my teeth (3 times a day), flossing, shaving my face, etc.
But since getting ME/CFS, I don't seem to want to do these things. I now brush my teeth if I am lucky once a day, rarely floss, and only shave now once a week. I now let my beard grow into long stubble, and then when it gets a bit too long after a week or so, I shave it off with a hair clippers. But prior to developing ME/CFS, I used to do a nice close wet shave every day. An d I used to enjoy the grooming process. Now when I shave, it is a chore, and not something I enjoy at all (although this might be due to my anhedonia, which prevents me for enjoying even the very simple pleasures in life; grooming is usually enjoyable or pleasurable).
I imagine this reduction of grooming behavior might be less prevalent in women, who tend to be naturally better at personal hygiene and grooming. Men more easily slip into "pig" mode, in my experience.
Among the males here, has anyone else noticed a reducing in grooming habits?
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Undisclosed
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I'm with Duncan -- 'Sickness behavior' has many many negative connotations. Joe average wouldn't look beyond the label 'behavior'. It is negative and leaves us open to further -- CBT-like quackery. ME needs to be taken seriously.
Hip
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At the moment, the idea that sickness behavior may be involved in ME/CFS is just one of dozens of other theories of ME/CFS. I don't think Joe average generally follows the various comings and goings of ME/CFS theories, so even if this term did have some negative connotations, the general public is not going to come across this term, unless like many ME/CFS patients, they spend years delving into the science of ME/CFS.
It seems to me a bit premature to start worrying about possible negative connotations of this obscure scientific term that happens to be linked to ME/CFS in just one single study that likely few people outside of the ME/CFS community even know about.
And any scientist interested in this vagus nerve infection theory is going to fully understand that the mental state changes found in sickness behavior are due to well-defined biological causes, and so will understand that the sickness behavior theory views ME/CFS as a disease with a physical cause.
Now if someone were proposing that instead of SEID, we call it say chronic sickness behavior disorder, then I would agree that this would not be a good idea, due to possible negative connotations of malingering.
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Hip
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Wouldn't the use of an IL-1β receptor antagonist like anakinra be more of a "suck it and see" situation? When it comes to immunosuppressants or anti-inflammatories, it not just a case of trying them out, and empirically observing whether the infection is worsened or improved?
SOC
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I got some clarity on this point from Dr Klimas today. She told me that clinically ME/CFS and GWI are indistinguishable, or nearly so, but as soon as you look at the systems biology work that's being done by Broderick, you can see that they are very, very different. Which is very interesting. Clinically identical (essentially) and fundamentally very different.
Basically, compared to a healthy person, the systems biology network of a patient with GWI shows many more connections meaning their bodies are doing a lot of work-arounds to deal with some failed pathways. OTOH, the systems network of a PWME looks like swiss cheese, with many holes showing failed pathways and no ability to work around the losses.
lansbergen
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That is interesting.
Again I think we are totally barking up the wrong tree thinking this is an infectious disease.
Unless all or most other autoimmune diseases turn out to actually be fundamentally infectious will there be any chance this is an infectious disease.
- 75% women / 25% men ratio
- Relapse/remitting architecture
- Sleep disturbances
- Neuroinflammation
- Typical onset in mid 30s
- Improved symptoms during pregnancy
- Stress/infection trigger onset and symptoms
- And more...
Unless all or most other autoimmune diseases turn out to actually be fundamentally infectious will there be any chance this is an infectious disease.
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