Could high TNF-alpha be causing my symptoms? // Could Humira help?

[ljimbo423]

True, unless high TNF is due to an aberrant immune reaposne that never got switched after the acute phase off and is now causing symtoms.

Hi Jesse- I think the chances of that are very slim. Many of the studies I have read say the immune dysfunction seems to be caused by some kind of pathogen.

However, that doesn't mean you might not be able to get symptom relief from trying to modify tnf-a.

Jim

 

[halcyon]

I think that study tested cells out of serum in a nutrient bath. Ron Davis says there is something in the serum causing mitochondrial dysfunction.

Yes that's true. It does make it less likely that it's anything in the serum that caused what they saw in the Lawson Stanford study.

Ron Davis says cells are normal outside of patient serum. The Lawson study shows they are abnormal outside of patient serum.

 

[halcyon]

True, unless high TNF is due to an aberrant immune reaposne that never got switched after the acute phase off and is now causing symtoms.

Perhaps. But if it was causing you symptoms it seems like they would be more viral or flu like than anything else.

 

[Jesse2233]

This is interesting, and contradicts Fluge / Mella's study

A pilot study of tumour necrosis factor fusion protein, etanercept (a substance which blocks the interaction of TNF with its cell surface receptors) was done by K Lambrecht et al (Minneapolis). 6 CFS patients were given an 8 week trial of etanercept injections. Significant reductions were observed in the severity of fatigue, muscle pain, headache and lymphodynia. Exercise tolerance was improved. This lends support to the theory that proinflammatory cytokines maybe involved in the pathogenesis of CFS, and this should be further studied in a placebo-controlled trial.

http://www.me-ireland.com/AACFS Conference2001.htm

 

[Jesse2233]

I've decided to up the LDN dosage, add in high quality CBD oil, double my curcumin, and try very low dose bupropion to see if I can get TNFa lower. If not I may speak to my immunologist about Enbrel or Humira

 

[Jesse2233]

@halcyon @Hip

This is an interesting study I'd not seen before. Shows a link between enteroviruses, TNFa, and autoimmunity

Viral infections frequently result in the production of autoantibodies. In most cases, these autoantibodies are low-affinity IgMs that exhibit extensive cross-reactions. Sometimes these virus-triggered immune responses progress to a pathogenic autoimmunity to form autoimmune disease. To delineate the mechanisms determining induction of autoimmune disease, we have investigated in detail a model of autoimmune myocarditis induced in genetically susceptible mice by infection with a cardiotropic strain of coxsackievirus B3. We found that the autoimmune sequelae of the viral infection can be simulated by immunization of the susceptible mice with murine cardiac myosin. In both models of the disease, the determination of whether to progress from a contained viral myocarditis to a pathogenic autoimmune response is made within hours after induction of infection and is characterized by production of a few key cytokines, including IL-1beta and TNFalpha. Many of the lessons learned from study of these models are applicable to human myocarditis and dilated cardiomyopathy.

https://www.ncbi.nlm.nih.gov/m/pubmed/18357776/

 

[Gingergrrl]

No, honesty I'm not sure I have except maybe once in the first month. It's either not a feature of whatever I have, or I don't overexert enough to get to that point.

I do feel a general worsening the few times I go beyond 3000-3500 steps a day, but I wouldn't say it's exactly flu-like in terms of feeling like I have a virus. The only times I feel "ill" in that sense is after IVIG

Wow, this is exactly like my situation in that PEM is either not a feature of what I have or I do not overexert enough to get to that point. I obviously cannot walk 3000 steps and use wheelchair but the first part of my illness, I was still working full-time (Jan 2013 to March 2014) and I did not stop driving and start using the wheelchair until Oct 2014.

So the wheelchair was not a part of my life until I was sick for almost two years and I was 100% overexerting myself back then. At that time it got harder and harder to stand and walk until within seconds I would get dyspnea and angina type pain (which has improved with IVIG to a level that has already exceeded my wildest expectations).

But after IVIG, I get a delayed flu-like immune reaction with fever, muscle pain, chills, headache, etc, and truly feel ill. It is triggered by the IVIG but has never been triggered by exertion for me. I wish I knew what this meant. I found this thread trying to remind myself what TNFa was (and I think it is a pro-inflammatory cytokine)?

 

[Gingergrrl]

@Hip or @Jesse2233 I think this is the right thread to ask this question, if I had high TNFa (but was never tested so I do not know) and had an enterovirus (or another virus) in my heart, could the 13 months of high dose IVIG have cured this virus?

Or if I really had a cardiac virus, would I have constantly felt flu-like symptoms and had a fever which I did not (vs. having POTS, tachycardia, hypotension, dyspnea, angina type pain, etc). I hope this question makes sense!

 

[Jesse2233]

@Gingergrrl I have the same question myself! Don't know if there's a good answer though I suppose you could retest the enterovirus titers

 

[Gingergrrl]

@Gingergrrl I have the same question myself! Don't know if there's a good answer though I suppose you could retest the enterovirus titers

Maybe I will re-do the ARUP tests some day but my titers on the two positives were never 1:320 which Dr. Chia considered active. One was 1:80 and one was 1:160 and the others were negative. And I was never IgM positive for Parvovirus and only IgG positive (and we re-ran the IgM and did a PCR to be certain and all were negative). My IgM positives, that stayed positive for several years, were to EBV, VZV, and HSV. Just including in case this is relevant.

 

[JES]

I'm currently using both LDN and Bupropion. The first time I tested Bupropion, I experienced some great improvements over the first week, but then begun to feel sicker, so had to stop. This reaction often happens to me with immune suppressing / anti-inflammatory supplements, so I'm trialing it now again on a lower dosage than what is typically used for antidepressant purposes.

From my understanding, Bupropion is a lot safer in the long run than biological TNF-alpha inhibitors, as it does not block TNF-alpha fully and hence does not come with the increase cancer risk that these biological inhibitors carry. Frankly when I first read about Bupropion, I was baffled why doctors don't prescribe it as first choice to reduce TNF-alpha, but I guess it's not a good business to sell a thirty year old drug that has the same effect as newer, more expensive ones... Same story as with LDN.

 

[ukxmrv]

I did OK on Humira (also had high TNF-a) and in particular less viral symptoms and less pain.
Unfortunately, I could only afford around 4 injections. It was such a long time ago I can't remember the number but have had so few positive reactions to drugs that I remember the good reaction well.

 

[halcyon]

@halcyon @Hip

This is an interesting study I'd not seen before. Shows a link between enteroviruses, TNFa, and autoimmunity

Thanks that chapter looks really interesting, I'll have to revisit it when my brain isn't so fried.

The association of viral infection and autoimmunity has been remarked upon frequently, but the mechanisms underlying the association have not been well understood (Rose and Griffin 1991). Viral infections regularly initiate the production of autoimmune responses, but only rarely are they pathogenic. Several different mechanisms have been proposed to explain virus-induced autoimmunity. Sometimes the responses result from cross-reactions between antigens of the virus and those of the host, so-called molecular (or, more properly, epitope) mimicry (Rose and Mackay 2000; Cunningham 2004). Recent investigations have emphasized the frequent occurrence of molecular mimicry in nature, both at the level of antibodies and T cells. Virus infection may amplify preexisting, naturally occurring autoantibodies and selfreactive T cells. This amplification of our innate autoimmune repertory may result from the adjuvant effect of the viral infection itself (Rose and Afanasyeva 2003; Fairweather et al. 2005). Viral infection can also release and alter normally isolated, inaccessible self-antigens. Thus, we are not surprised when many viral infections, or even immunization using live vaccines, increases the levels of preexisting autoantibodies. The problem facing the investigator is to determine whether these common autoimmune consequences of viral infection are harmless or pathogenetic; that is, whether they contribute in some meaningful way to a disease process. If such evidence can be mustered, the disease can be regarded as autoimmune within the definition developed above. There are still very few well-established instances of a human autoimmune disease resulting from a particular viral infection.

I know people like Prof. Edwards are critical of molecular mimicry, these other hypotheses sound plausible.

 

[Hip]

If anyone wants to try some TNF-alpha inhibitors (other than the standard ones like etanercept, which is expensive and has a black box warning regarding serious side effects), the following all have potent TNF-alpha inhibiting effects in vivo:

Noopept in rats reduces TNF-alpha by 50%, at intraperitoneal doses of 5 mg/kg (equivalent to a human oral dose of around 6 mg of noopept). 1

Wellbutrin (bupropion) — inhibits TNF-alpha, IL-1beta and gamma interferon. 1

Macrolides roxithromycin, erythromycin and clarithromycin inhibited TNF-α in rats at oral doses of 40 mg/kg (equivalent to a human dose of around 500 mg). 1 (full text). NOTE: Roxithromycin is the only macrolide antibiotic that crosses the blood brain barrier, and it also the most potent TNF-α inhibitor out of these three antibiotics.

Stinging nettle leaf "Supplementation of stinging nettle in humans has been shown to decrease LPS induction of inflammatory mediators, triggering an 80% reduction in TNF-α and a 99% reduction in IL-1β" 1 2

Spironolactone — inhibited by 70–90% the release of TNF, lymphotoxin, interferon-γ, granulocyte-macrophage colony-stimulating factor and interleukin 6. 1

Vinpocetine — potently inhibits TNF-alpha-induced or LPS-induced up-regulation of proinflammatory mediators, including TNF-alpha, IL-1beta in mice, at intraperitoneal doses of 10 mg/kg (equivalent to a human oral dose of around 80 mg of vinpocetine). Vinpocetine must be taken with food, otherwise its bioavailability is very poor. 1

An article on the use of etanercept in ME/CFS is found here: Etanercept (Enbrel)

And in this article it notes:

Etanercept - We started a clinical open-label phase-II study on weekly subcutaneous etanercept (a TNF-alpha inhibitor). Only four patients were included, and we decided to stop the trial because two patients had a clear worsening of ME/CFS symptoms, while two were unchanged (no response). Ideally, we should have included additional patients to gain experience for a more solid conclusion; we however decided to stop the trial.

Another article of interest:

Etanercept TNF-A inhibitor helps CFS after 5 weeks, one person found

"I was in a “pre-study” with Enbrel back in 2000. I have CFS-moderate. For the first weeks-nothing. Week 5-8 I felt wonderful. Not completely normal, but SO much better. I cried when I had to stop at 8 weeks and found out the cost of Enbrel. What I would not give to see Enbrel further studied and approved for CFS treatment."

I have noticed mild improvements in symptoms taking vinpocetine, and erythromycin.

I had an amazing 2 week near remission from brain fog and fatigue taking Wellbutrin, but the beneficial effects wore off after exactly 2 weeks, and I could not repeat these effects, even after taking a break and trying Wellbutrin again months later.

 

[Tunguska]

Hi, well I can tell you I'm almost sure high TNF-alpha has been a significant part of my constellation of symptoms. But it seems it would be very common. Although wellbutrin does lower it as far as I was aware it might be simply due to increased cAMP: http://forums.phoenixrising.me/index.php?threads/wellbutrin-bupropion-lowers-tnf-in-crohns.19768/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314873/ "Studies observed that bupropion lowers the level of an inflammatory mediator TNF-alpha (by increasing the intracellular cAMP that inhibits TNF-alfa synthesis)"
and so simple things like caffeine or forskolin could achieve this as is reported, and potentially any nonspecific PDE inhibitors. I use pure caffeine constantly (coffee is horrible) and slowly increasing dosage over time. I've been delaying trying wellbutrin (and twenty other things) because can't find a reason it would be better than caffeine and caffeine is so cheap it's almost free and fine after you adapt and balance it out. Probably will try Vinpocetine before wellbutrin.

 

[Jesse2233]

@Tunguska interesting, any benefit from caffeine?

 

[Tunguska]

Yes, keeps me alive and able to do some mental work. It's two-faced and it can worsen my high BP and vasoconstriction (this happens through several mechanisms for me I'm certain, so it's all confounded) and some skeletal issues if used alone, so I have to offset it with other things (magnesium/steroids/aminos/gaba/enos), but with those it helps both brain clear-headedness and body stamina/energy severalfold more reliably than anything else. The worst moments were just because I forgot magnesium existed. In last months I've started upping caffeine dose (400-600mg/day, in a kind of bid to eliminate dependence on less sustainable drugs, I guess that's my point or something) my gut has calmed down significantly more, but impossible to know exactly what that's about.

 

[Jesse2233]

Very interesting. How did you come to believe your TNFa was high? And does the stack above help or hinder OI (if that's one of your symptoms)?