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TH2 Immune System Dominance and Heterogeneity in ME/CFS

Discussion in 'Other Health News and Research' started by Marco, May 27, 2010.

  1. richvank

    richvank Senior Member

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  2. natasa778

    natasa778 Senior Member

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    Many who are verbal will often complain of fatigue ... The other problem, apart from lack of words to describe how they are feeling in most, is that it may be tricky to describe something that is all you've known in your life (as in 'fatigue as a natural state'). Another thing to throw in here is that very often tiredness in children very manifests as hyperactivity!

    But have a look at this:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584230/?tool=pubmed

    Some comments are idiotic (“Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism” -as if they really measured clinical abnormalities in a large group of asd patients to be able to say what is “common” and what is “uncommon” in idiopathic autism.... They are probably referring here to oliveira study, which was far from definite and measured only a few markers... http://www.ncbi.nlm.nih.gov/pubmed/15739723)

    but this part of the paper really jumps out:
    Nineteen patients exhibited constitutional symptoms, especially excessive fatigability...
  3. richvank

    richvank Senior Member

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    Hi, Natasa.

    Thanks very much for posting these links. I'm very interested in similarities and differences between autism and CFS, because I think that understanding them may help to improve the treatment of CFS. As you are probably aware, there is more research going on into autism than into CFS, and I think the CFS community stands to benefit from the autism research if we understand the similarities and differences.

    Thank you again!

    Rich
  4. jeffrez

    jeffrez Senior Member

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    The TH1/TH2 imbalance theory (or observation) was pioneered by Dr. Cheney years ago. This is nothing new. I didn't read the thread yet - am I missing something?
  5. Marco

    Marco Old blackguard

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    Hi Mr Kite

    I didn't claim that the TH1/TH theory was new - I mention de Meirlier and others in my posts.

    What may be 'new' in my musings was that I suggested that ME/CFS was a condition of immune system dysregulation which may be triggered by a wide range of stressors - thus explaining the hereogeneity in onset, duration etc.

    Perhaps just a change in emphasis - but it changes the focus away from finding the 'one pathogen' to considering ME/CFS as a systemic dysfunction. Treatment therefore should revolve around correcting the TH2 dominance and whatever other ongoing stressors there are. I proposed considering PWC's within a matrix of no viral load/high viral load and TH2 dominant/not TH2 dominant.

    For example if someone presents with high viral titres but is not found to have an immune shift to TH2 dominance then by my definition they have an untreated viral infection but do not have ME/CFS.

    The first three posts cover it.
  6. Marco

    Marco Old blackguard

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    Hi Diesel.

    From what I can pick up on the net Zadaxin appears to be doing all the right things including reducing oxidative stress.

    As it appears to be well tolerated, a clinical trial would be interesting, particularly if they also tried it on a group with no apparent current viral infection.
  7. jeffrez

    jeffrez Senior Member

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    Like I said, Cheney has already discussed this extensively. The agents he's identified for shifting the TH1/TH2 balance are Kutapressin, Isoprinosine, pine cone extract, heparin, some kinds of transfer factor, and some other peptide product called lumbricus. If you know of any others, please let us know, as most of those either are difficult to obtain (kutapressin, heparin) or not readily available anymore (pine cone extract - though one could make one's own, perhaps). regards
  8. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    Mold Toxin and Pig Liver


    Kutapressin is made out of pig liver. And since pig liver comes up as really bad on Cheney's Echo Terrain Mapping machine (which he uses to gauge the positive or negative effects of various substances), I suspect that he's not recommending Kutapressin any more.

    Buffalo liver comes up as one of the more positive substances on the machine. This suggests that CFS sufferers do indeed need liver support, and that it's something about pig's liver in particular that's bad.

    A number of studies (below) have implicated the susceptibility of pigs' livers to trichothecene mold toxins. The grain and other foods that pigs eat often are contaminated with these mold toxins, and pigs' livers apparently don't handle them very well.

    Buffalo, on the other hand, eat free-range grass. Mold contamination assumedly would not be an issue with that.

    If I am correct in my contention that CFS sufferers are hypersensitive to toxic mold, it would make sense that they would react poorly to it wherever it is found....including the remnants of it in pigs' liver products.

    To my knowledge, no one has attempted to take a mold-contaminated object to Dr. Cheney's office to see how that would affect them on the ETM machine. It would be interesting to see how that experiment would come out.

    I'm willing to place a sizable bet that an item that was really contaminated would create the biggest negative energy backflash of anything that's ever been recorded on that machine of his. Would anyone like to take me up on it?

    Best, Lisa

    *

    Dll S, Schrickx JA, Dnicke S, Fink-Gremmels J. Interactions of deoxynivalenol and lipopolysaccharides on cytokine excretion and mRNA expression in porcine hepatocytes and Kupffer cell enriched hepatocyte cultures. Toxicol Lett. 2009 Oct 8;190(1):96-105. PMID: 19607891


    The effects of deoxynivalenol (DON) on the mRNA expression of cytokines and inflammation-related genes, as well as the cytokine secretion of porcine hepatocytes and Kupffer cell enriched hepatocyte cultures (co-cultures), were investigated in the absence or presence of LPS.

    DON and LPS acted in a synergistic manner with regard to a significantly increased mRNA expression of TNF-alpha in hepatocytes exposed to 500 nM or 2000 nM DON, or non-significant increase in co-cultures after 3h of exposure.

    TNF-alpha supernatant concentrations were increased due to LPS but did not reflect the synergistic effects with DON as observed at mRNA level.

    IL-6 mRNA in hepatocyte cultures at 6h paralleled the TNF-alpha supernatant pattern at this time point. In co-cultures and hepatocytes, a DON dose dependent induction of IL-6 mRNA was detected in cells not exposed to LPS. Supernatant concentrations of LPS-induced IL-6 were significantly decreased by 2000 nM DON in both types of cell cultures. Also the mRNA expression of the anti-inflammatory IL-10 was increased by DON to various degrees depending on DON-dose, stimulation with LPS and time point of measurement. After 6h, expression of iNOS was only induced by 2000 nM DON, but not in LPS treated cells.

    Even if mRNA induction was not paralleled by related supernatant concentrations of TNF-alpha, IL-6 and IL-10 under the conditions of the present investigations, it was clearly demonstrated that DON has the potential to provoke and modulate immunological reactions of porcine liver cells.

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    Mikami O, Yamamoto S, Yamanaka N, Nakajima Y. Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol. Toxicology. 2004 Nov 15;204(2-3):241-9. PMID: 15388250

    Deoxynivalenol (DON) is one of the major mycotoxic contaminants of grains, which causes reduced weight gain in pigs.

    The cytotoxicity of DON to porcine hepatocytes was examined in this study.

    These results indicate that DON induced apoptosis through the caspase-3 activation pathway and caused functional disorder in porcine hepatocytes.

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    Meissonnier GM, Laffitte J, Raymond I, Benoit E, Cossalter AM, Pinton P, Bertin G, Oswald IP, Galtier P. Subclinical doses of T-2 toxin impair acquired immune response and liver cytochrome P450 in pigs. Toxicology. 2008 May 2;247(1):46-54. PMID: 18355953

    This study was designed to investigate the effect of subclinical doses of T-2 toxin on liver drug-metabolizing enzymes and the immune response.

    Pigs fed 1324 or 2102microg T-2toxin/kg feed exhibited reduced anti-ovalbumin antibody production without significant alteration to specific lymphocyte proliferation.

    The livers of pigs exposed to T-2 toxin presented normal cytochrome P450 content, UGT 1A and P450 2B, 2C or 3A protein expression, and glutathione- and UDP glucuronosyl-transferase activities.

    However, P450 1A related activities (ethoxyresorufin O-deethylation and benzo-(a)-pyrene hydroxylation) were reduced for all pigs given T-2 toxin, with P450 1A protein expression decreased in pigs fed the highest dose. In addition T-2 toxin exposure reduced certain N-demethylase activities.

    The results of this study confirm the immunotoxic properties of T-2 toxin, in particular toward the humoral immune response.

    The reduction of monooxygenase activities, even though the liver presented no tissue lesion or lipid peroxidation, suggests possible deleterious interactions of T-2 toxin with these enzymes.

    *

    Pestka JJ, Smolinski AT. Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health B Crit Rev. 2005 Jan-Feb;8(1):39-69. PMID: 15762554


    At the molecular level, DON disrupts normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation, and apoptosis.

    Relative to toxicity, there are marked species differences, with the pig being most sensitive to DON, followed by rodent > dog > cat > poultry > ruminants.

    Chinese epidemiological studies suggest that DON may also produce emetic effects in humans.

    With respect to chronic effects, growth (anorexia and decreased nutritional efficiency), immune function, (enhancement and suppression), and reproduction (reduced litter size) are also adversely affected by DON in animals, whereas incidence of neoplasia is not affected.
  9. Marco

    Marco Old blackguard

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    That's all right. I'm not trying to claim bragging rights - just sharing some things that occured to me from reading up on some of this stuff.

    As I said before, most researchers seem to identify immune imbalance and then go looking for the bug that causes it. Hence conflicting reports of which bug is the culprit. More productive I thought to concentrate on the key issue of immune dysregulation.

    And on the basis that I'm only speculating, I'm not prepared to try any substance outside of of harmless supplements unless there is proof positive of the problem and the solution.

    All I'm willing to try on the basis of 'my' theory are supplements like glutathione, zinc, ALA and grape seed extract that are reputed to support or modulate the immune system. I might even add a little cumin (or a nice curry) following Diesel's lead.
  10. jeffrez

    jeffrez Senior Member

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    That's fine, I just didn't see his name anywhere and thought it deserved mention. Just be careful with the grape seed extract because it can damage the liver if your cytochrome system can't handle it, and ALA can be dangerous in a backfire, and even redistribute heavy metals if you do backfire. GSH precursors can backfire, too - NAC, for example. With problems in sulfur metabolism not uncommon in CFS/MCS patients, supplements like that can be risky. And zinc tends to deplete copper, as you probably know, which could be problematic depending on your mineral profile. Just things to watch out for, gl.
  11. helsbells

    helsbells Senior Member

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    Hi rich

    I have Aspergers, ME and EDS III and severe MCS/food Intolerances plus IC so I copped for the lot :Retro mad: I am AS diagnosed but with siblings who are also strongly suggestive, interestingly though no one else as ill as me in family so I drew the short straw but they do show less physical stamina although unlike me don't seem to be cognitively impaired.
  12. natasa778

    natasa778 Senior Member

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    Hi Helsbels!
    ... there seems to be at least 2 or 3 more persons with both Aspergers and CFS/ME on this forum...
  13. helsbells

    helsbells Senior Member

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    Hi natasa778
    it doesn't surprise me really as their paths seem to cross quite often, doesn't bother me per se (its the rest of the list im gunning for :D) but interesting for what it might suggest neuro immune wise.
  14. readyforlife

    readyforlife Senior Member

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    I went to my doctor yesterday and he talked to me about a peptide injection called SAM-PD. It does something to stop of slow down the over active TH2. He would have me do one injection every month for a year. He just came back from a conference I think in Belgium, where there was alot of talk about this Peptide. I asked him what he new about Peptide T and he told me he didn't know to much about it. I was on Heparin for about six months and It really helped because it slowed down the TH2.
  15. helsbells

    helsbells Senior Member

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    How did you take heparin/how often - I did this and didn't notice much but as I was doing as IV (may have been a push - didn't seem to takelong) only doing every few months over a couple of days - which may not have been often enough.
  16. readyforlife

    readyforlife Senior Member

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    Helsbells, I injected Heparin twice a day for six months. I just got tired of having to do it everyday. I'm thinking about going back on it again because I haven't been feeling that great.
  17. Marco

    Marco Old blackguard

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    Duly noted and many thanks Mr Kite. BTW - what is a backfire - apart from the schoolboy obvious?

    PS - I should have said tumeric (curcumin) not cumin.
  18. helsbells

    helsbells Senior Member

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    I can see why the amounts I was injecting weren't doing much, it would have been a bigger amount (I assume) but 3 days out of 3 months! Do you use an insulin syringe subcutaneously? i am interested because I did tolerate heparin and I don't tolerate much at all.
  19. jeffrez

    jeffrez Senior Member

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    I found these other lists of substances that allegedly shift the TH2 imbalance.

    Omega-3 fatty acids, monounsaturated fats found in olive and hazelnut oils, vitamin A cod liver oil, l-Glutamine, Silica, digestive enzymes, friendly intestinal flora or soil based organisms (SBOs), ginseng (Red Korean or concentrated Siberian Ginseng extract), chlorella (spirulina and some other sea vegetables may have similar benefits), thyroid hormones, garlic (raw or aged extract), l-Glutathione (or products that raise levels), DHEA or AED (androstendiol), UV-A light, vitamin E, transfer factor (antigen specific) - protein immunomodulators extracted from colostrum, colostrum, low dose naltrexone, IP6, lentinian and certain other mushrooms, Thymus extracts, licorice root, dong quai, beta 1,3-glucan, noni, neem, gingko biloba, exercise, water (to aid detoxification), a positive attitude, the ability to forgive and be compassionate, and having long-term goals.

    ------------------------------------
    Supplements that enhance TH1 immunity.

    -Pineextract (web)
    -Zinc
    -Earth Dragon (amazon)
    -LDN
    -Thymic immune Factor (lef)
    -Astragalus
    -AHCC may increase Natural Killer (NK) Cell activity
    -NK immune (source naturals)
    -IP6
    -Rice Bran Arabinoxylan Compound
    -Epicor
    -beta glucans
    -Coconut/Olive oil
    -Increased Glutathione
    -Glutamine
    -Colostrum
    -Ginkgo
    -Garlic (Fresh and aged)
    -Chlorella
    -Noni
    -neem
    -DHEA
    -Silicon
    -IP6
    -Vitamin E
    -Heparin
    -Transfer factor
  20. slayadragon

    slayadragon Senior Member

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    The Ability of Mold Toxin to Inhibit Viruses

    Just to expand our thinking, here are a few articles suggesting that Stachybotrys demonstrates antiviral activity against Influenza A and other viruses.

    Perhaps the fact that our systems are full of mold poison keeps us from getting colds and flus?

    (I don't think it's just current exposures, since I've not heard of anyone pursuing extreme avoidance who's started getting colds/flus again either.)

    I actually think there's something more to this phenomenon than just the poisons killing off the viruses.

    But the idea that this might be contributing is an interesting thought.

    Best, Lisa

    *

    Minagawa K, Kouzuki S, Yoshimoto J, Kawamura Y, Tani H, Iwata T, Terui Y, Nakai H, Yagi S, Hattori N, Fujiwara T, Kamigauchi T. Stachyflin and acetylstachyflin, novel anti-influenza A virus substances, produced by Stachybotrys sp. RF-7260. I. Isolation, structure elucidation and biological activities. J Antibiot (Tokyo). 2002 Feb;55(2):155-64. PMID: 12002997

    Two novel compounds, stachyflin and acetylstachyflin, have been isolated by solid-state fermentation of Stachybotrys sp. RF-7260.

    Stachyflin showed antiviral activity against influenza A virus (H1N1) in vitro with an IC50 value of 0.003 microM. Acetylstachyflin was about 77-fold less active than stachyflin.

    *

    Mari Nakatani, Masahiko Nakamura, Akiyuki Suzuki, Munenori Inoue, and Tadashi Katoh. A New Strategy toward the Total Synthesis of Stachyflin, A Potent Anti-Influenza A Virus Agent: Concise Route to the Tetracyclic Core Structure. Org. Lett., 2002, 4 (25), pp 44834486. PMID: 12465918

    A new strategy directed toward the total synthesis of stachyflin, a potent and novel anti-influenza A virus agent isolated from a microorganism, has been presented through the enantioselective synthesis of the tetracyclic core structure. The synthetic method features a BF3Et2O-induced domino epoxide-opening/rearrangement/cyclization reaction as the key step.

    *

    Minagawa K, Kouzuki S, Tani H, Ishii K, Tanimoto T, Terui Y, Kamigauchi T.. Novel stachyflin derivatives from Stachybotrys sp. RF-7260. Fermentation, isolation, structure elucidation and biological activities. J Antibiot (Tokyo). 2002 Mar;55(3):239-48. PMID: 12014438

    Stachybotrys sp. RF-7260 was found to produce stachyflins, novel anti-influenza virus agents, under solid-state fermentation conditions. Feeding DL-lysine to a culture of Stachybotrys sp. RF-7260 induced the formation of the novel compounds, SQ-02-S-L2 and -L1, and feeding DL-valine the formation of SQ-02-S-VI and -V2. The structures of these metabolites were determined by detailed 2D NMR analyses in comparison with acetylstachyflin. SQ-02-S-L2 and -L1 have the lysine moiety and SQ-02-S-V1 has the valine moiety. SQ-02-S-V2 has an amidine moiety instead of the lactam moiety in acetylstachyflin. SQ-02-S-L2, -L1 and -V1, substituted on the lactam amide hydrogen, displayed only a low level of the antiviral activity. However, deacetyl SQ-02-S-V2 showed potent antiviral activity similar to stachyflin.

    *

    Tani N, Dohi Y, Onji Y, Yonemasu K. Antiviral activity of trichothecene mycotoxins (deoxynivalenol, fusarenon-X, and nivalenol) against herpes simplex virus types 1 and 2. Microbiol Immunol. 1995;39(8):635-7. PMID: 7494505

    The effect of trichothecene mycotoxins, deoxynivalenol (DON), fusarenon-X (FX) and nivalenol (NIV), on plaque formation of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in HEp-2 cells was examined.

    The 50% effective concentrations (EC50) of DON, FX, and NIV for HSV-1 plaque formation were 160, 56, and 120 ng/ml, respectively. Those for HSV-2 plaque formation were 94, 26, and 50 ng/ml, respectively. These three mycotoxins showed about 2-fold higher selectivity to HSV-2 than to HSV-1. Plaque formation of HSV-1 was not inhibited with trichothecenes at concentrations completely inhibiting plaque formation when cells were treated during virus adsorption period or 15 hr before infection.

    These results indicate that trichothecenes affect replication of HSV-1 after virus adsorption, but not before or during virus adsorption to the host cells.

    *

    Sawadjoon S, Kittakoop P, Isaka M, Kirtikara K, Madla S, Thebtaranonth Y. Antiviral and antiplasmodial spirodihydrobenzofuran terpenes from the fungus Stachybotrys nephrospora. Planta Med. 2004 Nov;70(11):1085-7. PMID: 15549667

    Two known spirodihydrobenzofuran terpenes (1 and 2) were isolated from a mycelium extract of the fungus Stachybotrys nephrospora BCC 3900. Compound 1 (Mer-NF5003F or stachybotrydial) exhibited potent antiviral activity (the IC50 value of 4.32 microg/mL) comparable to the standard drug, acyclovir, while compound 2 was inactive against the HSV-1 virus. Both 1 and 2 possessed antiplasmodial activity (IC50 values of 0.85 and 0.15 microg/mL for 1 and 2, respectively), and were not toxic towards the Vero cell line. A regiospecific conversion of the dialdehyde 1 to the lactone 2 proceeded simply under acidic conditions.

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