Results of Cytokine Multiplex 18 Report

[Hip]

One of the drugs you took, zidovudine, can cause mitochondrial myopathy, though in long term use:
Mitochondrial Myopathy Caused by Long-Term Zidovudine Therapy — NEJM
Mitochondrial myopathy associated with chronic zidovudine therapy in AIDS
Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage

Symptoms of various mitochondrial myopathies:
Types of Mitochondrial Myopathies

 

[PhoenixBurger]

Yeah Mitochondrial / DNA damage is one of the 3 things that have been on my radar since this started. Whether in bone marrow or systemwide. Mitochondrial toxicity is associated with cancer development and numerous other "system failures" of undefined origin. Basically you damage mitochondria, you can end up with dysfunction. Especially because those damaged cells replicate more damaged mitochondria. Included in this item is lipid membrane damage by the drugs. Not just AZT. Included also is damage to muscle cells. Solution: Treating myself like I have mitochondrial disorder. CoQ10 daily (ubiquinol), PQQ, ALA, RLA, B vitamins, and exercise for mitochondrial biogenesis. I spent a few weeks reading all the techniques used by those born with mitochondrial deficiencies, etc.

I found mention that Kaletra can cause muscle fasciculations/twitching and nerve damage.

HIP - if I am dealing with inflammatory immune syndrome of some sort, why are *all* of my inflammatory markers not only normal, but many are significantly lower than a normal person's is? SED rate, IL-6 ... ANA .... serum RA ... nearly every single one of them is on the low end of low. I have zero inflammation in my body according to all testing that has been done.

 

[Hip]

Treating myself like I have mitochondrial disorder. CoQ10 daily (ubiquinol), PQQ, ALA, RLA, B vitamins, and exercise for mitochondrial biogenesis.

Sounds like a good strategy.

A while ago I also tried taking lots of mitochondria supporting supplements, to see if it would help my ME/CFS (in my case, it did not help that much). The supplements I used are the following:

Mitochondrial Cocktail daily supplements:
Deprenyl (selegiline) 5 mg
Rhodiola rosea 350 mg
Lecithin 1200 mg
Lithium 5 mg
7-keto DHEA 50 mg
Leucine 3 grams
Glutamine 5 grams
Niacinamide 1000 mg
Ginkgo biloba (24%) 60 mg
Piracetam 2 grams
Q10 200 mg
Magnesium malate 1500 mg
Monolaurin (or coconut oil)
Taurine 1000 mg
Acetyl-L-carnitine 800 mg
Alpha lipoic acid 250 mg
Pyrroloquinoline quinone (PQQ) 20 mg
Benfotiamine 80 mg
Carnosine 1000 mg

Some of these are to support mitochondrial function; others are to support mitochondrial biogenesis. I believe the average lifespan of a mitochondrion is around one month, so your cells are making new mitochondria all the time.

The main promoters of mitochondrial biogenesis (the making of new mitochondria) are nitric oxide, and tri-iodothyronine (T3 thyroid hormone). Possibly some of the nitric oxide inducing body-building supplements may help.

if I am dealing with inflammatory immune syndrome of some sort, why are *all* of my inflammatory markers not only normal, but many are significantly lower than a normal person's is?

Why are you saying that when your IL-2 and IL-17 are sky high? Both are pro-inflammatory cytokines.

I know that your SED rate, etc does not show inflammation, but this is the same in ME/CFS: inflammatory markers like C-reactive protein can be normal in many ME/CFS, but if you look at cytokines in ME/CFS patients, you notice that there is inflammation.

I think in the case of ME/CFS, this is because the infections are chronic, low-level, smoldering infections, and so they don't show up on the radar unless you test the cytokines.

 

[PhoenixBurger]

Why are you saying that when your IL-2 and IL-17 are sky high? Both are pro-inflammatory cytokines.

I see now that "2" is traditionally viewed as pro-inflammatory. Not sure why it's not listed as such on my report. But I'm told that IL-6 and others are the "traditional" pro-inflammatory cytokines, and 17 is definitely listed on my report under "Anti-Inflammatory". *All* of the proinflammatory markers listed were normal, or low. Not a single one was high on the results. *All* of the markers listed as antiinflammatory on the report, were normal or high. This is causing confusion. Except that I realize sometimes each item plays both sides of the fence. However there are accepted inflammatory markers, and none of mine were elevated.

http://www.nature.com/nri/journal/v2/n1/fig_tab/nri702_F4.html

I know that your SED rate, etc does not show inflammation, but this is the same in ME/CFS: inflammatory markers like C-reactive protein can be normal in many ME/CFS, but if you look at cytokines in ME/CFS patients, you notice that there is inflammation.

Okay but here's the thing. I could be wrong, but I don't consider myself a CFS patient. I expected to see numerous indications of autoimmune disease because of my IRIS theory. But not only are all of my blood labs normal or low for immune inflammation, but all my immune markers are as well. This makes it very difficult for me to grasp what is going on, despite all the info you have provided. My understanding with CFS is that they have a struggling immune system due to chronic reactivations. Is that me too? Or am I mister autoimmune? Because it sure doesn't look like it.

I think in the case of ME/CFS, this is because the infections are chronic, low-level, smoldering infections, and so they don't show up on the radar unless you test the cytokines.

Isn't this exactly what Dr. Rey is telling me that I have?

One other note. When I thought I had Lyme, i was put on Doxy high dose. Doxy is a potent anti-inflammatory, and I swear I never felt better. It was deceiving, thinking that I had maybe killed off some Lyme. But Western Blot came back negative, as did C6 Peptide and PCR. So when I stopped the Doxy, all hell broke loose. My muscles and entire body felt inflamed and aching and just plain "wrong". It was a very very bad day. Laying in bed almost hurt. Turns out Doxy inhibits TnFa (which is listed as pro-inflammatory on the labs I got back). http://www.ncbi.nlm.nih.gov/pubmed/21350981 Maybe back then things were way out of whack, and one by one, things are falling back into place, so TnFa is now "normal" on my labs. I just don't know. I am still using your plan of attack once the cancer screenings are complete however. With suppressing the 17.

Will be speaking with the Doctor in a few minutes. I am afraid the entire conversation is going to be about Coxsackie and telling me I have mild viral reactivation. And that I should take the Equilibrant. I don't know what im going to say.

 

[Hip]

Interesting about doxycycline. I often take TNF-alpha inhibitor supplements, and I find they help reduce the irritability symptoms that I often get (irritability is a common symptom in ME/CFS, and even more so in autism, and irritability makes you feel like sh*t, as you find you get annoyed with everything).

I have a list of a couple of dozen TNF-alpha inhibitor supplements. But by far the most potent supplements are:

Cat's claw — a remarkably potent inhibitor of TNF-alpha production 1 2
Vinpocetine — potently inhibits TNF-alpha. 1
Taurine — significantly reduces TNF-alpha 1

It might be worth trying these to see what benefits they might offer.


It is difficult working out what are the pro- and what are the anti-inflammatory cytokines, because the roles of these cytokines are not always fixed.

Did you read this study which I posted earlier in this thread, where it says that the effects of high IL-2 are: TNF production, lymphocytic infiltration of multiple organs, multiple organ edema, hepatic dysfunction, leukopenia, and thrombocytopenia. So IL-2 seems to have quite a few negative effects.


I know you are likely not a ME/CFS patient. And don't worry, you are not the only one who is having great difficulty in grasping what is going on with them: that's the normal state of affairs on this forum. Even the expert researchers don't really know if ME/CFS is an autoimmune disease, or a brain and central nervous system condition, or an immune dysfunction disease, or an infection-driven condition, or a toxin triggered disease, or a low blood flow illness, or an ion channelopathy, or an autonomic nervous system imbalance, or a gut dysbiosis problem, or a combination of all of these.

 

[PhoenixBurger]

Just got off the phone with the Doctor. She explained in some detail her theory on each of the IL's. Though I didn't catch all of it, the general gist that my pro inflammatory cytokines are low or below "low" is indication to her that I have experienced burnout. Naturally the whole time she's talking, I am thinking to myself of the 14 months of misery I have endured with something going haywire inside of me. Burnout sounds about right. But I have no idea exactly what my immune system has been doing the whole time.

She feels strongly that I have reactivation of Mono despite the fact that the mono reactivation antibody is in the 50-75% range (which she has identified as the ideal range on every single other test result on the paper). She feels that CMV is also on the table, which I have known for several months. But which numerous doctors have told me would never cause bodywide muscle twitching to this extent, for this long. Such a syndrome is clearly considered autoimmune in nature, or paraneoplastic. I didn't feel comfortable challenging her, or even saying a word for that matter. In the end, what good will it do anyways, to make your doctor annoyed with you. Been there, done that, never served any good purpose.

She still wants me to boost my immune system.

She feels I need to fight off the Epstein Barr that I don't believe I even have active in me right now. And she feels I need to fight the coxsackie that I have no evidence is even currently activated. And she feels I need to try and get the CMV down from 1.1 to below 1.0. That much we can agree on. Boost my immune system? I told her I was terrified to do that because it brought back all my inflammation and every single problem I have had since this started. Instead of saying "Well maybe you're right then, maybe you're dealing with immune overactivity and we should *calm* your immune system instead" ..... instead she said "Well then take a quarter tablet of the immune booster instead of half a tablet".

:thumbdown:

I'm not the doctor with 30 years experience. She is. But the discussion of IRIS seems to have evaporated into thin air. When I asked how it is that I have neuropathy and symptoms of nerve damage, demyelination, and neurodegenerative problems (bodywide muscle twitching) - all of which are associated with Autoimmunity .... she said that herpes viruses can infect the spinal fluid and cause twitching. Especially herpes viruses, of which I apparently have a couple. She hesitated a few times as she said "Ive ... seen ... twitching ... before with this ... type of thing". She seemed very unsure of herself when she said it, and honestly I doubt she's seen twitching like this, for this long. But its true that on the HSV1 and 2 forums, you will see many reports of twitching being caused by those viruses. Usually however its short term. It doesnt last 9 months, and go literally all day long....

My clinical situation has been completely ignored throughout this entire process. Symptoms have been barely asked about, and almost never discussed. The only thing has been the bloodwork. My clinical presentation hasn't played a role in the decision making whatsoever, and that bothers me. Quite a bit. The only thing that remotely jives with the "viral reactivation" theory, in light of my actual *symptoms* ... is that my health seemed to improve dramatically, in direct correlation with the lowering of CMV IgM. In direct correlation with the CMV acute infection being successfully fought down by my immune system.

Put another way - as my immune system began to calm down. None of my actual *symptoms* have been symptoms of CMV.

Hip Is it possible that the HIV antivirals caused numerous reactivations, my immune system got seriously overtaxed, began going crazy, maybe even started causing nerve damage and other auto-immune-like symptoms, because it was fighting off these viruses? Because my symptoms don't match the viruses AT ALL! That is the very reason I thought I had IRIS. The form which the immune system THINKS these viruses are active but they arent. And the symptoms you get are that of an overactive immune system.

 

[PhoenixBurger]

And Hip - what about the theory of cytokine storm and possibly taking an ACE inhibitor?
http://en.wikipedia.org/wiki/Cytokine_storm

The only reason I would even think of this is because one of my only abnormal blood tests has been elevated ACE ....

 

[heapsreal]

If u think it is an over reaction of your immune system, have u spoken to your doc or has your doc considered a short course(3-5 days) of prednisone to calm down this inflammation? Maybe something like this can help reset things back to normal.

I dont quite understand how u can tell the difference between different symptoms and it being viral or not etc. Many of the symptoms from an infection come from the immune system anyway. I just say this because generally many of use with cfs/me have many strange symptoms that arent specific to one particular illness/diagnosis. This could be why your doc wont guarantee what your symptoms are from.

Some symptoms are from a hit and run injury from an infection, so possibly chasing after the cause is not going to help but maybe need to start trying different symptomatic treatments. Treating the nerve pains etc with anticonvulsants or similar treatment may reduce the possible damage done to them and possibly only needing this treatment for a set time?? This is all hypothetical though?? This can be done while still searching for the cause??

Cheers!!!

 

[PhoenixBurger]

I dont quite understand how u can tell the difference between different symptoms and it being viral or not etc. Many of the symptoms from an infection come from the immune system anyway.

Exactly. I don't know how one can tell the difference either. I was hoping to clarify that during my phone call with her, but I failed to get any meaningful discussion on that started.

I tried to ask about our conversation regarding Immune Reconstitution Inflammatory Syndrome, because it seems to have evaporated into thin air. I sought out immune testing so I could establish that this was happening, or rule it out, but ... the focus seems to be on Pathogens without any mention of IRIS. I do know that I have "burnt out" immune markers from "months of overactivity". And elevated immune markers showing current overactivity.

Yet they seem to only be focused on pathogens. Nothing else. So maybe when presented with an inflamed immune system, they will always see it through "pathogen-colored-glasses". I don't know. I'm concerned that maybe the "need" for it to be viral reactivation, is causing some "stretching" in the lab interpretation.

Why? Because I don't see any real viral activity in the bloodwork. Negative coxsackie IGM is being called currently active, and I don't know that it is. EBV reactivation antibody dead center in the "normal" % range shouldn't be an indicator that I have reactivated EBV. A barely positive CMV igm with negative PCR's wouldn't indicate viral activity. So what's left to support the "viral reactivation" theory? Not much.

It seems to me at that point you would actually talk to me about my symptoms. Unfortunately the topic of my symptoms has not even been brought up. When I have tried to mention it, countless times, it seems to be quickly dismissed. None of the interpretations in the bloodwork have included consideration of my symptoms. In the presence of unclear lab work, symptoms should be the most relevant factor, shouldn't they?

When I pushed a little further, pointing out that my symptoms are not that of CMV, nor Coxsackie, nor EBV ... but of nerve damage, demyelination, and motor neuron agitation ... she said she's "heard of" viruses like these getting into the spine and causing such symptoms.

So here I sit with no confidence in either direction.

To confuse this further, I should point out: One form of IRIS is simply the mass-reactivation of previously resolved viruses. So its possible I've spent the last 14 months fighting back a ton of known, and unknown infections that did reactivate. But I already knew that. The immune testing was supposed to give me more evidence in one direction.

 

[Kati]

SOC - Well remember I am probably not a CFS patient. I did endure months of unexplained fatigue and countless other symptoms that had no rhyme or reason, but most of that has passed. It was during those really rough months that I set up the appt with Rey - and then had to wait 6 full months to see her.

By the time I did, my situation had evolved into something more reminiscent of autoimmunity. So I expected my results to not quite match up with the typical ME patient. I have never felt that I am dealing with a struggling immune system due to viral overload, but the very opposite. And my results being opposite of yours may have some relevance.

I didn't have an IL-10. She didn't put any notes on the side, but the pre-written text I see there is greek to me

I am positive on Coxsackie A - IGG but negative on IGM. I can not determine if that means acute or paste infection. Usually IGM has to be positive for acute, no? I am still acute with CMV. Darn thing won't dip below "1". Been hovering there for 3-4 months now. Equilibrant is not smart for people with autoimmune issues, so I need to figure out if I am acute with Coxsackie. I will tough it out if I am. Otherwise I should avoid the stuff like the plague.

Regarding IL-2, as I understand it, the presence of IL-2 prevents autoimmunity. Therefore my high level of IL-2 may indicate that my body is struggling against autoimmunity. Trying to squash it. They actually use IL-2 injections for people with autoimmune disorders, to calm things down. So you may be right, my high IL-2 may be a sign that I am pre-autoimmune. I hope it doesn't become autoimmune

hi Phoenix, I would like to commenton your interpretation on what a result is low or high, and what is normal.


In my opinion, when a test result is within range, it should be interpreted as normal, and at best, "lowish or highish".
In my books, a results should be interpreted "low or high" if it deviates slightly from the range. For instance, the range of a certain test being 5-15, your result is 20, then it's high.

A very high result, for the same test with a normal range of 5-15 would be 50.

i mention this because when a test is within range, it is perceived as normal by physicians. Also, some of my our of range tests are not being seen as worrisome, for example I always have an out of range absolute red blood cell count (always high)

Also note that the liver enzymes, as an example, would be noted as very high by counting how many times higher than normal it would be, for instance, say ALT's highest range value is 50, if someone's value is 150, then it's 3X the upper limit. So having a value of 53 would not warrant getting too excited about even though it's out of range, and I know doctors don't get excited about that.

My Il-12 and 13 have been totally out of range one of them having been 20X the upper limit at some time in the past. And yet, we are not exactly sure what it means,whether these cytokines fluctuates, what exactly makes it better, and whether it matters.

One more comment about NK cell function, (which you are not reporting). According to Quest, a normal result if from 8-170. That is a wide range of normal if you ask my opinion. What is the true range for a healthy person not fighting a viral infection, and does this value is affected according to age, sex and diseases? There has got to be something more precise...

Best wishes, K

 

[Hip]

No time at the moment to respond, but regarding muscle twitching (fasciculation), looking into benign fasciculation syndrome might possibly gives some leads. There is a BFS forum HERE.

 

[PhoenixBurger]

Hip
Beat you to it again. Been posting there for months already. They dont discuss possible causes. They just reassure eachother that its not ALS. I came here out of frustration at the lack of scientific and exploratory discussion there. Let me know your response to the above when you are able. Thanks!