Pulmonary Fibrosis May Be Caused By Endotoxin (LPS)

Discussion in 'Scientific Studies' started by haidut, Jul 23, 2018.

  1. haidut

    haidut Member

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    Ray spoken and written at length about endotoxin (LPS) and its role in virtually all chronic conditions. Mianstream medicine vehemently denies that LPS is an issue, except possibly for people with liver disease. But in thoses cases, the claim is that endotoxin may cause fever and diarrhea but never an actual chronic disease like Alzheimers or systemic sclerosis. I posted a number of recent studies acknowledging the role of LPS in neurodegenrative disease, CVD, systemic sclerosis, dementia, osteoporosis, RA, MS, etc and all of these studies show that endotoxin exerts most of its negative effects through the TLR4 receptor. Blocking TLR4 was shown to be therapeutic in many of these cases. Recently, Pfizer started running clinical trials with an antiserotonin drug called terguride for a number of fibrotic disease, all linked to endotoxin and TLR4 overactivation. One of these conditions is pulmonary fibrosis, which is currently considered incurable and rapidly lethal.
    The study below shows that TLR4 antagonist can actually treat the condition when established and prevent it from happening int he first place. Interestingly, the same authors previously established that systemic sclerosis (scleroderma) is another condition driven by endotoxin and a TLR4 antagonist is therapeutic.
    https://raypeatforum.com/community/...o-endotoxin-blocking-tlr4-can-treat-it.13428/

    Perhaps more importantly, the scientists discovered that scleroderma and pulmonary fibrosis are basically the same disease, which further emphasizes the systemic nature of fibrotic conditions. Some of my friends who work in clinical trials have noticed the same trend for "autoimmune" conditions - i.e. there is a recent push to combine RA, Lupus, Sjongren, psoriasis, Crohn's disease, UC, etc into a single "syndrome" so that the same drugs can be used for all such conditions. This is driven exclusively by desire for more profits since a drug like Humira can now be used on all such conditions and the company does not have to seek separate drug approval for every single disease. But as an unintended consequence it will drive more and more doctors into the camp that all chronic conditions are systemic and other systemic causes like low thyroid function will also have to be addressed.
    So, it looks like official science is slowly wisening up to the role of colonic bacteria and endotoxin in chronic diseases but don't expect a public admission any time soon. Pfizer's trial with terguride is very low key and Pfizer refuses to comment on it when asked. The fact that Pfizer still sells SSRI drugs probably has something to do with this desire to keep things quiet, at least for now.
    As far as practical measures, aside from antibiotics and charcoal, TLR4 antagonists should also help. We have discussed TLR4 antagonists on the forum before but some of the better known ones include emodin, Benadryl, cyproheptadine, ketotifen, etc.

    JCI Insight - TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung
    Blocking Innate Immunity Protein May Treat Select PF Patients, Study Suggests

    "...TLR4 is associated with chronic inflammatory conditions, and researchers are exploring approaches that might block its effects. However, whether blocking TLR4 could be effective against fibrosis remains unknown. The research team has previously shown that the fibrotic skin and lungs of patients with scleroderma (a chronic disease that affects connective tissue, and is also characterized by fibrosis development) had higher levels of specific DAMPs. The investigators also revealed their common localization to myofibroblasts containing TLR4. These cells release collagen during the fibrosis development. Work in mice also showed that an absence or lack of working TLR4 protected from fibrosis induced in these animals."

    "...Findings revealed that the amount of MD2 and TLR4 messenger RNA — which contains the instructions to make proteins — was higher than usual in skin biopsies from scleroderma patients. The data also showed increased expression of TLR4-responsive genes, called a TLR4 gene signature, in a subset of patients. These genes were associated with inflammation and wound healing. Finally, the team found that selectively blocking MD2 with a small molecule named T5342126 abolished fibrotic responses in vitro and in patient-derived skin cells. Importantly, this molecule also prevented and reversed fibrosis in three mouse models. Results also showed that TLR4-deprived fibroblasts — cells will function in ways similar to myofibroblasts and are involved in fibrosis — were protected from skin and lung fibrosis. “Together, results from these human [cell] and mouse studies implicate MD2/TLR4-dependent fibroblast activation as a key driver of persistent organ fibrosis,” the investigators wrote. “Our study opens a new door into fibrosis by looking at it as an aberrant innate immune response and suggesting a novel approach to treat it,” Varga said."
     
  2. Blossom

    Blossom Moderator

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    I sincerely appreciate you bringing all of this information about probable causes and treatments for autoimmune diseases and related issues to the forum. I remarked in another thread recently that medicine seems to have little to no explanation and only toxic treatments are currently available. This information explains in part why my flares have been pretty mild since discovering Peat in comparison to other people I know with similar issues who are around my age who and require strong pharmaceutical interventions. It's particularly heartbreaking to see coworkers who are fairly young suffering from a whole host of terrible side effects from the medication they take in order to be able to work yet they are considered the fortunate ones because they aren't disabled yet. It's a difficult dilemma but at least we can learn about various ways to try to improve the situation on this forum.:):
     
  3. OP
    haidut

    haidut Member

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    What flares are you getting, if you don't mind sharing?
     
  4. Blossom

    Blossom Moderator

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    Sure, just old symptoms that I gave up on getting a formal diagnosis on years ago. Some symptoms similar to IBD (none atm), and some often attributed to MS and sjogrens but I'm managing really well with everything. Low dose naltrexone helps a ton but I don't like to stay on it too long. Of course I think I'm primarily doing so well from thyroid, progesterone and other Peat inspired lifestyle changes and a few of your supps!
     
  5. OP
    haidut

    haidut Member

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    A friend of mine was recently declared to be in "permanent remission" (not even sure what that means, and how it is different from "cured") from MS. Her brain lesions disappeared and it made her doctor send her for 3 separate MRIs to 3 different locations because he could not believe his eyes. She has been using ketotifen and progesterone for about a year, after her previous MRI showed deterioration of brain lesions. She can't use thyroid as it gives her insomnia and tremors, but she seems to be doing quite well on these two. The "downside" to this story is that the insurance company kicked her out of disability status without any warning and it caused quite a bit of financial distress. Technically, they should not have done that because MS is officially an incurable, progressive disease so an already disabled person stays disabled for life. But the doctor filed some paperwork and the "permanent remission" caught their eye.
    However, she is thrilled to be healthy again and does not care much about insurance any more :):
     
  6. Regina

    Regina Member

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    so maybe it explains the thinking that joint pain occurs with 'too-low estrogen'.
    https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12462
    In the skewed conventional view of collagen, hyaluronic acid and fibroblasts.
    In another thread, I believe you had mentioned that during the reversal of fibrosis old injuries can become painful (sorry if I am mis-attributing).

    I tried to open an ampicillan capsule into diamant to smear on my neck lymph and over my spleen. The grainy powder did not dissolve (made kind of sticky sand that won't absorb).
    Just another thing to try to throw at my (undoubtedly related)finger symptoms.

    Great posts, haidut! Thx!!
     
  7. Blossom

    Blossom Moderator

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    That's fantastic! Do you know if she cycles progesterone? I noticed I do best when I'm using it continuously even if I vary the dosage. Going a full week without any seems too long for me atm. It's so tricky figuring the best dose when you're in peri menopause/ menopause and everything is changing so much.
    Unfortunately I can pinpoint my mild flares to times I stopped progesterone altogether.
    Interesting link @Regina. I saved it to read in detail when I have some extra time.
     
  8. OP
    haidut

    haidut Member

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    She does not cycle the progesterone, AFAIK. And I think she uses a combination of oral and topical. She said she averages about 50mg daily.
     
  9. Blossom

    Blossom Moderator

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    Thanks, It's good to know what's working for others.
     
  10. Momado965

    Momado965 Member

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    Does this mean bromocriptine and cabergoline do NOT cause pulmonary fibrosis regardless of dose and pulmonary fibrosis is actually because of stress and its stressful hormones?
     
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