I strongly believe this has a lot to do with immune system modulation. Though I wouldn’t risk touching Fin again. There’re other parameters that may favorably affect immune system. I’m now working in accordance with the Th1/Th2 shift theory. I seem to exhibit symptoms that are tied to Th2 dominance and I’m working to resolve the root causes. IMO, some of these causes include the gut dysbiosis, nutritional imbalances, chronic infections, and certain stressors.
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Thats alot of immune markers, both pro-inflammatory and anti-inflammatory.
All of these biomarkers of immunity can be tested.
This would be a good way to put it while still staying accurate, because this could go in different directions. Not only that, there could be different responses while on a drug like Fin or Accutane and then after stopping the drug.
Obviously with Fin the immediate conclusion would be androgens or antiandrogens are modulating the immune response. I think there was even a study looking at a dry eye model that said as much.
With Accutane there is alot more data and possibilities as far as to what might be regulating what.
One example, Good or bad?
Portrait of an immunoregulatory bifidobacterium
"promotion of retinoic acid metabolism by B. infantis was a key regulatory feature of this bacterium"
There is increasing interest in the administration of microbes or microbial metabolites for the prevention and treatment of aberrant inflammatory activity. The protective effects associated with these microbes are mediated by multiple mechanisms involving epithelial cells, DCs and T cells, but most data are derived from animal models. In this addendum, we summarize our recent data, showing that oral consumption of Bifidobacterium infantis 35624 is associated with enhanced IL-10 secretion and Foxp3 expression in human peripheral blood. In addition, we discuss the potential DC subset-specific mechanisms, which could contribute to DCREG and TREG programming by specific gut microbes.
Immunomodulation by Bifidobacterium infantis 35624 in the Murine Lamina Propria Requires Retinoic Acid-Dependent and Independent Mechanisms
Whats il-10 btw?
IL-10: The Master Regulator of Immunity to Infection
The Interleukin-10 Family of Cytokines and Their Role in the CNS
Interleukin-10 (IL-10) is generally considered to be the quintessential immunosuppressive cytokine, and its ability to resolve inflammation and promote wound repair at peripheral sites is well documented.
…
Great read, thanks for sharing. I’ve been having issues for years on end and it took me a long time to learn of this intricate relationship between symptoms remission and immune system behavior. I never made the link before because I was so distacted and focused on other things that I thought were responsible. It all started with me trying to figure out why I had symptoms of low libido, brain fog, depression, lethargy, achy joints, night sweats. I did numerous blood tests and E2 always turned out very low. Then I tried everything to raise it yet to no avail. I had more tests done and learned that I had some sort of adrenal insufficiency (high cortisol; low DHEA). So I did more research and decided to take DHEA and BOOM E2 went up quickly. Then I learned that having high Cortisol leads to low DHEA. So I read up on causes for “adrenal fatigue”. All scientific articles brought up chronic inflammation being a major problem for adrenals. I did more tests and found that I had high inflammatory markers that are mostly tied to issues with the gut. It felt like “light switched on” because I started to remember how good I felt when ever I’m on antibiotics onviously for other irrelevant reasons. So I had taken Rifaximin for two weeks and BOOM I’m feeling 1000% better! But the effect would slowly phase out upon discontinuation.
This is why I did 3-4 rounds of antibiotics and I’d get the same kind of response. I tried numerous Probiotics with different outcomes. So I bombarded my guts with antibacterial spices/herbs, diet restrictions (Low FODMAP) and loaded on resistant starch in addition to Bifido. Infantis, Lactobacillus gasseri, Bifido. Longum, S. Boulardii… basically all histamine degraders and anti-inflammatory strains because I displayed a shift in Th1/Th2 with Th2 dominance. I had scary herx. reaction that seemed like a die-off.
I’m in a much better place now than all those years. I’m still trying to figure out the immune system disorder to beat this forever. Sorry for the wall of text.
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I just wanted to confirm for comparison you have taken this same exact strain of 35624 bifido longum?
This is known as Align in the States (not sure where your at). They came out with a higher dosage awhile back at 5 billion per capsule. I had trialed this for a period of time and still have mixed thoughts, so I would be curious about another opinion. I think you might have been the one that mentioned you thought Vitamin A helped you, which is ironic of course.
Im looking into the book price of testing both il-8 and il-10 serum through labcorp.
Im a little curious about these right now.
On il-8, I saw this just mentioned. I’d take this a step further and look at possible inflammation in the entire pelvis region. Obviously if anything like this was going on you could forget about normal sexual function.
Interleukin 8 (IL-8) - a universal biomarker?
Marker for Prostatitis
Increased IL-8 levels were detected in expressed prostatic secretions (EPS) of chronic prostatitis (CP) [6]. In addition, higher IL-8 levels were detected in prostatic secretions, ejaculate and serum from patients with latent CP [7]. Thus increased expression of cytokines in EPS may serve as a valuable diagnostic marker for CP. Other cytokines such as IL-2 and IL-10 were also detected in EPS [6]. A panel of assay including cytokines detection in EPS can serve as good marker for CP [6].
Man, this worries me. I just had a mild fever with mostly dry coughs. Only a bit of phlegm came out.
I never had a cold or flu this mild.
Align (1Billion CFU) was the one. I used it for about 3 weeks. I’d like to assume that I didn’t suffer pelvic inflammation except for the occasional soreness in pelvic muscle/joints but this is probably due to heavy leg workout. My understanding is that Interleukin-8 (IL-8) induces neutrophil migration to sites of infection (or inflammation). Please correct me if I’m wrong.
That said, I mostly experience symptoms such as stuffy nose (probably from swollen turbinates.), headaches, and eczema/skin itchiness.
“Proinflammatory interleukins (IL-1β, IL-6, and IL-8) are elevated in patients with allergic rhinitis and have been shown to promote the activation of immune cells as well as to enhance expression of receptors for cell adhesion molecules (eg, selectins, integrins).19These events, along with IgE synthesis and eosinophil/basophil priming, collectively contribute to inflammation, venous engorgement, nasal hyperreactivity, and symptoms of allergic rhinitis, including congestion”
I’ve had several CBC labs done and Eosinophils count was elevated possibly indicating allergy. I wonder if Neutrophils count can be used as an indicator for IL-8 abnormalities. My high Eosinophils count (along with allergy symptoms) instigated after being on BioGaia L. Reuteri (histamine producing strain) alongside high consumption of beef liver (High Vitamin A content). It feels as if L. Reuteri was able to colonize my gut OR high Vitamin A (hypervitaminosis) was inducing increased immune reactions. I ate a lot of beef liver because I had high Vitamin D level, which I initially thought may have depleted liver retinol.
Both Vitamin D and Vitamin A appear to posses immunomodulatory properties.
Allergic reactions hit the adrenal hard resulting in Adrenal insufficiency. This is from AdrenalFatigue.org:
"Adrenal function plays an important role in allergic reactions. Most allergies involve the release of histamine and other pro-inflammatory substances (substances that produce inflammation). Cortisol, one of the primary hormones produced by the adrenal glands, is a strong anti-inflammatory (a substance that reduces inflammation). In fact, the amount of cortisol circulating in the blood is a key factor in controlling the level of inflammatory reactions in the body. For this reason, healthy adrenal function plays an important role in mediating the histamine release and inflammatory reactions that produce the symptoms experienced with allergies.
When the adrenals are fatigued, it is more difficult to produce the additional amounts of cortisol necessary to adequately counteract the inflammatory allergic reactions. People going through times of adrenal fatigue may notice that they seem to have more allergies or their allergies seem to get worse. Conversely, the more histamine released, the harder the adrenals have to work to produce enough cortisol the more fatigued they may become. It is therefore not surprising that people with food and environmental allergies commonly tend to experience adrenal fatigue as well. This can set up a vicious cycle of reduced cortisol allowing histamine to inflame the tissues more, leading to deepening adrenal fatigue as well as to bigger allergic reactions.
Actively supporting your adrenal glands and eliminating or reducing your exposure to foods and other substances that cause allergic or sensitivity reactions can help break this cycle as well as strengthen adrenal function. Food allergens can interfere with daily functioning and become a profound stress on your adrenals, so it is important to track down and eliminate these food sensitivities and allergies in order to both decrease your allergy load and promote adrenal health."
I’m aware that adrenal fatigue is not recognized by the scientific bodies but this goes perfectly in line with my n=1 case. Normalizing inflammatory cytokines based on your individual findings to restore adrenals is the way to go.
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Some good info. I actually have eosinophilic esophagitis thats been diagnosed twice now years apart by endoscopy based on a biopsy showing elevated eosinophils.
I believe this is somewhat rare and I might have had this long before Accutane, not sure.
I am allergic to all airborne allergens recently reconfirmed by skin prick testing.
I also have tested high or have elevated ige antibodies. This could fall in line with allergies.
@guitarman01
This could help your diagnosis further:
“Vitamin A deficiency decreases the IgA, IgG1, and IgE responses but increases the IgG2a response to viral infection (6, 7, 8). The underlying pattern of cytokine production by APCs and T cells is consistent with these effects on Ab production: vitamin A deficiency increases constitutive IL-12 production by macrophages (9), and during secondary in vitro stimulation of lymphocytes with Ag, vitamin A deficiency increases IFN-γ production, but decreases IL-4 and IL-5 production (10). Conversely, supplemental treatment with vitamin A or retinoic acid (RA)4decreases IFN-γ and increases IL-5, IL-10, and IL-4 production (11, 12, 13). Thus, vitamin A deficiency biases the immune response in a Th1 direction, whereas high-level dietary vitamins may bias the response in a Th2 direction.”
It’s in my understanding that Accutane is a derivative of Vitamin A. Did you happen to take any Vitamin A in isolated form? Or through a multivitamin supplement? Or simply ate foods that are high in Vitamin A (e.g. beef liver)?
“Using vitamin A together with ISOtretinoin is generally not recommended. Combining these medications may increase the risk of hypervitaminosis A, a condition that stems from excessive vitamin A-related effects.”
I recall you had histamine intolerance symptoms when you had taken BioGaia L. Reuteri Probiotic. Histamine is also related to Th2 activation.
Yea, i’ll have to get back to you on some of this. Thanks.
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Yea, I think the L. Reuteri probiotic was a mistake. One of my main thoughts on this was a possible overproduction of gastric acid because of h2 receptor activation, but idk.
I tried blocking histamine receptors individually h1,h2 at elevated doses and that didnt help either.
Its also might have more of a certain type of anti-inflammatory profile or immunosuppressive, which isnt always beneficial. Looking at all of this, it would be about a balance of pro-inflammatory vs anti-inflammatory immune regulation.
Going back to Vitamin A and D though, I started a thread on this awhile back.
Another type of immunity.
IL-17: a key player in the P. acnes inflammatory cascade?
Propionibacterium acnes induces an interleukin-17 response in acne vulgaris that is regulated by vitamin A and vitamin D
Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes has a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of T helper 17 (Th17) and Th1, but not Th2 responses in human peripheral blood mononuclear cells (PBMCs). P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA, and IL-17RC, and triggered IL-17 secretion from CD4(+), but not from CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naive CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6, and transforming growth factor-β-neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and D could be effective tools to modulate Th17-mediated diseases such as acne.
Nice find. Point is I’ve been on high dose Vitamin D before for its purported Testosterone boosting effect. My level went up to 57 ng/ml at one point and this happened to be the same period when I was at my lowest point (mentally as well as physically). I dropped Vitamin D and begun eating beef liver (~18,000IU Vitamin A/100g) and there was this “balance point” where my serum Vitamin D level went down to sub 40 ng/ml and I was still eating beef liver constantly and also begun taking high dose antibiotic Xifaxan (1600mg/d). I recall experiencing euphoric sensations like never before! My gut function was great too with no signs of inflammation.
Fast-forward, I took L. Reuteri and kept having much more beef liver and ended up getting histamine intolerance symptoms (eczema, hives, clicky joints, tiredness, headaches, GI issues, etc.). I think my liver retinol was too high level and this may have caused Th2 Dominance. I stopped beef liver and Vitamin D altogether.
I’m waiting to see if this could replicate those euphoric feelings. Mind you, I still have amazing days but I want more stabilization.
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Was this the two week course they advertise for ibs? Is this something you got a prescription for and covered by insurance? If not I thought I remember hearing the out of pocket cost for these pills was pretty high. Curious about this, thanks.
I took it only for 8 days because I was taking much higher dose than what my Doctor prescribed. Yep insurance covered it (fortunately) and yes it’s quite expensive!
This is why L. Reuteri (or any histamine increasing or sensitizing strains) is bad for us with Th2 Dominance:
“Histamine plays an important role in the pathogenesis of atopic asthma through differential regulation of T helper lymphocytes. Histamine enhances the secretion of Th2 cytokines such as IL-4 (interleukin-4), IL-5, IL-10 and IL-13 and inhibits the production of Th1 cytokines IL-2 and IFNγ (interferon-γ) and monokineIL-12. It has been shown that histamine can modulate the cytokine network through upregulation of PGE2(prostaglandin E2) and NO (nitric oxide). Histamine also affects cytokine production via H2 receptors and through the activation of PKA (protein kinase A).”
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Thanks.
When I was looking at this probiotic, I think they attributed activation of the h2 receptor for its immunosuppressive properties. I think histamine can actually have opposing effects depending on what receptor is activated. The h1 receptor can be considered pro-inflammatory for example.
I believe this bacteria actually sends out a metabolite that blocks h1 activation.
Regardless, for me this is maybe only something to learn from, yea something I wont be going back to.
Bad for us.
Here’s that dry eye model.
Evaluation of a novel dry eye model induced by oral administration of finasteride.
Im looking at this differently right now. Im looking at the immune response.
What you see in this study might be considered a “normal” immune response.
What should happen.
Identification, immune mobilization, clearance, healing.
All of these markers of immunity maybe should be looked at.
Looked at for any deficiency in this response.
The cytokine antibody array system identified increased B7‑2 (also known as cluster of differentiation 86), interleukin (IL)‑1β, IL‑4, IL‑6, IL‑10, matrix metalloproteinase‑8, Fas ligand, tumor necrosis factor (TNF)‑α and metalloproteinase inhibitor 1 levels in the lacrimal gland of the dry eye model. These cytokines were validated as candidate markers through the use of western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Both analyses confirmed a significant increase in proinflammatory cytokines, including IL‑1β, IL‑6 and TNF‑α, and anti‑inflammatory cytokines, including IL‑4 and IL‑10.
I am sure this is a tough question, but I need to ask. Are you Th1 or Th2 dominant? I’m sure there’s not an absolute answer because we may demonstrate Th1 and Th2 tendencies, but there’s usually a more dominant side. There’re ways to go about this and one would be to have direct test for inflammatory markers (Cytokines) if resources are available. Ferritin, CRP, and Antibodies tests may all prove usefulness. Paying close attention to symptoms can also be used.
Knowing the answer to that question may pave the way for a treatment modality. In my case, I needed to fortify Th1 to balance out Th2 and to do just that, I attempted the following:
- Avoid histamine Probiotics
- Limit high histamine foods
- Limit antioxidants use
- Take very little Zinc (balance it with Copper)
- Balance Vitamin A (liver Retinol) & Vitamin D level
- Support Adrenals
- Use Antibiotics (Prescription & Natural ones) for SIBO
- Reduce Stressors (Mental & Physical)
I’m now experimenting with resistant starch and soon Butyrate. I’d like to think the above was helpful. Oddly enough, I’ve seen some studies hinting that anti-inflammatory drugs (e.g. NSAIDS) may be useful. It’s not like I’m condoning their use since they do have their own share of nasty sides (Ulcers being one), but I’m kind of tempted to try low dose Celebrex for my shoulder tendonitis.
Well, when I see the term anti-inflammatory I might also be thinking of a substance having immune suppressive properties.
I started this thread looking at possible immunosuppressive properties of these drugs.
Even if I was to try to simplify your question even further and say do I feel like im more in a constant state of inflammation due to a type of autoimmunity or immunocompromised to some degree, I dont think I would be able to definitively answer that either.
I have been to a rheumatologist for all the common plethora of tests (and its alot) looking at possible inflammatory conditions, nothing really flagged.
There are though multiple studies and even real test results from post-drug patients indicating this ongoing possibility.
Neuroinflammation, pelvic inflammation, etc.
Even in a state of inflammation I think a type of immune deficiency could still be possible.
I would still maybe be looking at boosting immunity ultimately, without triggering autoimmunity.
I am going to be looking into testing the most major cytokines just like they looked at from that last study on Fin. These would be both pro and anti-inflammatory. Im guessing none will be that cheap out of pocket though. They could have limited diagnostic value, but could reveal anything abnormal as far as immunity is concerned, and then go from there.
I’ll have to look into this some more.
One thought or a simple marker is the lower average body temperature that seems to be a trend on here. I think I could include myself in this as well.
Maybe being able to raise that by just a degree or two could be a simple indicator of improved health and immunity.
Also th2 immunity isnt always a bad thing.
Il-10 should probably be looked at.
Its a broad immunosuppressant.
Again good or bad in our case?
Do we know?
Homeostasis might rest at il-10 driven immunity.
Evolution of Th2 Immunity: A Rapid Repair Response
^maybe forget the pathogen angle in the study, or realize a drug could also be considered a “pathogen”
Even allergies.
CD4 þ Th2 cells are directly regulated by IL-10
during allergic airway inflammation
https://www.nature.com/articles/mi201647.pdf?origin=ppub
This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating
the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.
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Still looking at this same immune marker for the moment.
It seems to be known as the most potent anti-inflammatory or immunosuppressive cytokine.
Not always a good thing btw, but going over some of the positives first of what i’ve come across.
IL-10 produced by macrophages regulates epithelial integrity in the small intestine
https://www.nature.com/articles/s41598-018-38125-x
These results suggest that in the absence of IL-10, tissue repair does not occur, in part due to unhindered effects of pro-inflammatory cytokines
Then looking outside the gut, although you could probably consider the oral cavity an extension of this.
Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases
and then you see how simply this could be modulated.
Probiotic-derived molecule may suppress fatal brain inflammation, preclinical study finds
https://www.sciencedaily.com/releases/2019/05/190514081740.htm=
Scientists explore how swallowing a ‘bacterial envelope molecule’ may prime your body to fend off viral infections
The study, published in Nature Communications on May 14, found that B. fragilis ’ bacterial envelope, PSA, brings forth regulatory T and B cells that suppress the immune system from overproducing harmful inflammatory responses triggered by herpes simplex virus infection. In other words, PSA reduced brainstem inflammation by promoting the appearance of IL-10 secreting regulatory T and B cells. IL-10 is a strong anti-inflammatory cytokine which creates a protective, anti-inflammatory response that prevents encephalitis