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The role of IP-10 in Chronic Fatigue Syndrome

Cinders66

Senior Member
Messages
494
I don't understand much the science of this , which looks possibly interesting on cytokines
Of the 5 MRC funded projects this was one which looked one of the most interesting, rather than an essentially sjogrens fatigue study and Carmine Parientes interferon one
I'm staggered that even in this that Oxford criteria and NICE criteria were used and that this was part funded by MEA who are supposed to be against both criteria. Do the charities have no influence on the criteria of studies they fund and who would have chosen this and why, is it the CMRC favoured approach? I'd thought this was the psychological schools criteria of choice and then the biological scientific research in uk like Newton or Bansal used fukuda etc .

We arent going to see Oxford retired and unhelpful Cochrane reviews promoting exercise based on Oxford criteria challenged like this.
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
@JaimeS, do you happen to know whether Ron Davis has tested Rapamune (sirolimus aka rapamycin) with CFS blood and his impedence measuring device?

What a coincidence; there is a paper sitting at my left hand that talks about rapamycin. I think we're thinking along the same lines, @nandixon, just quickly glancing at what's in your signature. We haven't tested rapamycin yet, so far as I'm aware.

Downregulation of MAPK is a reasonable tack to take on the surface; but it's involved in so many different signalling pathways that I'm tentative.
 

AdamS

Senior Member
Messages
339
I started looking into IP-10 inhibitors and found this interesting given the recent findings about the microbiome and subsequent discussion about probiotics:

Inhibition of TNF-induced IP-10 expression in IEC is mediated by a cell surface protein of L. casei
Further analysis of other clinically relevant probiotic strains, Lactobacillus plantarum 299v and E. coli Nissle 1917, revealed that the inhibition of TNF-induced IP-10 secretion is dose-dependent and a unique feature of L. casei (Figure 2A).

L. casei can apparently be found in drinks like Actimel & Yakult. VSL#3 can be bought online. I think E-coli Nissle is also known as Mutaflor and doesn't seem to have the same inhibitory effect on IP-10 as L. casei.

2a5dsw8.png


L. casei inhibits IP-10 secretion and triggers subsequent intracellular degradation of the chemokine
Figure 1, general protein translation and secretion was not impaired by the probiotic bacteria as indicated by normal or even increased secretion of other cytokines/chemokines like IL-6 (Figure 1A/B) or MIP-2 (data not shown). Western blot analysis of intracellular IP-10 protein levels revealed that TNF-induced IP-10 protein expression was not inhibited by L. casei at early time points (3h after costimulation). In contrast, the loss of intracellular IP-10 protein was detectable after 6 to 24 h of costimulation although it was not secreted into the cell culture supernatant (Figure 5A). This result demonstrated that initial TNF-induced IP-10 translation is not targeted by the probiotic bacteria suggesting that the observed loss of IP-10 protein is due to post-translational degradation.

It's a long paper...but may be useful: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0004365

Finally on a side note...I see that raised IP-10 is also associated with Hepatitis C and also patients co-infected with HIV. Would the anti-viral Ribavirin be useful for us too in this case?
 
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John Mac

Senior Member
Messages
321
Location
Liverpool UK
@AdamS Pardon my ignorance but most of this is way over my head, are you saying that taking L. casei will lower IP-10? which I assume would be a good thing if you have raised IP-10?

From the study:
Maximal Voluntary Contraction Force and self-reported fatigue both showed particularly strong associations with plasma IP-10 concentrations.
Muscle content of IP-10 mRNA was significantly elevated, suggesting that, at least in part, muscle was a source of this IP-10 but not the other cytokines.

I took part in the study and had a muscle sample taken and analysed so hoping they found IP-10 high.
I have tried probiotics before and they seemed to trigger my ME symptoms the following day but will give it another go based on these (potential) results.
 

AdamS

Senior Member
Messages
339
@John Mac

From what I understand, both L. Casei and VSL#3 have been shown (at certain doses) to inhibit IP-10.

Whether treatment with these probiotics would help us is something i'm not sure of. I'd proceed with caution at this stage if you've had bad reactions to probiotics in the past.
 

Hutan

Senior Member
Messages
1,099
Location
New Zealand
From what I understand, both L. Casei and VSL#3 have been shown (at certain doses) to inhibit IP-10.

That's interesting. Three of us in my family got ME in 2103. My daughter was prescribed VSL#3 by a paediatric gastroenterologist. My daughter mostly recovered, probably not completely, but certainly enough to live what looks like a normal life. My son and I remain very much affected.

I'm not really sure why my son and I didn't try the VSL#3. It wasn't particularly clear-cut, as in - 1. take the VSL#3, then 2. get better. After the first month of illness, my daughter was already not as sick as us and this was well before the VSL#3. Also, that first year in particular was a haze of just getting through each day as I was still trying to work (with my husband working overseas) and work out what was going on and support my children. So, maybe I missed the contribution of VSL#3.

Still, I expect that there isn't a lot of downside to taking the probiotic. I must get some and try.
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
From what I understand, both L. Casei and VSL#3 have been shown (at certain doses) to inhibit IP-10.

Whether treatment with these probiotics would help us is something i'm not sure of. I'd proceed with caution at this stage if you've had bad reactions to probiotics in the past.

Having specifically tried VSL-3 and had a terrible neurological response, I would NOT recommend. Powders appear terrible for me, but I have an enteric-coated capsule from Dr Ohirra's that works wonders. :)
 

eljefe19

Senior Member
Messages
483
Having specifically tried VSL-3 and had a terrible neurological response, I would NOT recommend. Powders appear terrible for me, but I have an enteric-coated capsule from Dr Ohirra's that works wonders. :)
Hi Jaime,
I have a message to pass to Prof Davis. I think Rapamycin needs to be a priority in testing. After reading a few accounts here of Rapamycin producing fast and drastic relief, I acquired some.
I am now three days into starting 1 mg Rapamycin, so take with a grain of salt, but I feel basically cured. I've tried probably 200 different supplements and medications so I don't think it's placebo effect that my brain fog is gone.
Thanks Jaime!!
___________________________________________________________________________________________


Dear Prof Davis,

I know you are hard at work but I think you should hear this.
I saw an account of a patient that was given the drug Rapamycin and they had very fast and very drastic improvements in their ME/CFS symptoms. From bedbound to active. Even exercising.

Then I saw a doctor in Dallas was using Rapamycin for ME/CFS and six or so patients had all had drastic improvement.
So, I acquired 1mg tabs of Sirolimus (Rapamycin). It's been three days since the first dose.

I have not felt this physically, and mentally well, in months or maybe years.

For example, my brain fog is greatly improved. I don't think that placebo could produce such an effect.

What I've learned is that Rapamycin inhibits mTorC1 and in the process this activates Akt. The Akt activation could explain the immediate relief felt from Rapamycin. Interestingly though, Rapamycin also inhibits chemokines that are high in ME/CFS, and also has suppressive effects on B cells and can remove pathogenic antibodies (not sure about autoantibodies). So it has three methods of action that may ultimately unblock the PDH enzyme and abolishes impedance in your experiment. I like those odds.

Thank you for all you do for our community, I'm truly grateful that you would take the time to read this.
God speed, signed;
eljefe19.
 

aimossy

Senior Member
Messages
1,106
Having specifically tried VSL-3 and had a terrible neurological response, I would NOT recommend. Powders appear terrible for me, but I have an enteric-coated capsule from Dr Ohirra's that works wonders. :)
Hi Jaime have you got a link to that specific one?
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
I have a message to pass to Prof Davis. I think Rapamycin needs to be a priority in testing.

I might even have a rationale too, even beyond MAPK, based off of that article I was telling you about before. :)

I just added information about probiotics here: http://forums.phoenixrising.me/inde...-now-how-it-helps-and-general-me-advice.1739/ :D

For those who prefer to cut to the chase:

10. Probiotics

So it's pretty clear that some probiotics are really a poor idea for some patients. However, for reasons I can't begin to speculate, a probiotic that's enteric-coated causes no untoward symptoms for me. The probiotic I take I can't begin to recommend enough, and was shocked I hadn't discussed it here, already; I've been taking it for at least a year, now. It's Dr Ohhira's Original Formula probiotic, and I take one in the AM, one around 2pm. Be aware, you should take it at least an hour before a meal, and at least two hours after a meal, or it will make you nauseated.

Note: despite our speculation here on PR, this has many of the same bacteria in it that have made me ill in the past, making me think it's not "lacate-producing" that's really the problem. Over many, many months, my digestion has improved to the point that I can eat (some) foods I once had issues with, including citrus, apples, potatoes, sugars (yes, there was awhile where I was on zero sugar, even fruit-sugar), and some nuts. Like the CoQ-10, this is a relatively expensive supplement, but it's worth it to me.

If I miss two doses, my gut starts to become very... loud. The company swears you only need ONE pill per day for ONE month to restore your microbiome and then you won't need their product anymore, but I guess we are special little snowflakes.

Other probiotics I've tried that have caused neuro flares include VSL-3 (which KDM recommended), fermented foods such as kim chee, D-lactate-free probiotics, and the list goes on. This brand is the only kind I don't react to. There is also an extra-strength version which I have never tried.

Finally, the same brand makes a version that produces glutathione in the gut. I find that it tends to help digestion and mood even -- but I saw no improvement over time from using it, just the same effect every time. With the Original Formula I've actually seen consistent gains, even though I return to having issues within a few dose-times if I run out.

-J
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,402
Location
Toronto, Canada
I am now three days into starting 1 mg Rapamycin,

Thanks for being n = 1 and for sharing your great response, gives us all hope.

Are you taking 1mg each day? Do you anticipate taking it every day, or will you stop and see what happens?

A quick search says I can buy it (in Canada) for $900 US per 1mg pill. Did you find a cheaper source?

Thanks.