#65

I think you’re right, it’s a very specific case. You need to understand all the pathways involved (“So many pathways, so little time”). ERK, AMPK, STAT3

The STAT3 gene is part of a family known as the STAT genes. These genes provide instructions for making proteins that are part of essential chemical signaling pathways within cells. When STAT proteins are turned on (activated) by certain chemical signals, they move into the cell’s nucleus and attach (bind) to particular areas of DNA. The STAT proteins bind to regulatory regions near genes, which allows the proteins to control whether these genes are turned on or off. STAT proteins are called transcription factors on the basis of this action.

Through its regulation of gene activity, the STAT3 protein is involved in many cellular functions. It helps control cell growth and division (proliferation), cell movement (migration), and the self-destruction of cells (apoptosis).

The STAT3 protein is active in tissues throughout the body. It plays an important role in the development and function of several body systems and is essential for life. In the immune system, the STAT3 protein transmits signals for the maturation of immune system cells, especially T cells and B cells. These cells help control the body’s response to foreign invaders such as bacteria and fungi.

In addition, the protein is involved in the regulation of inflammation, which is one way the immune system responds to infection or injury, and it plays a role in cellular processes that promote allergic reactions.

https://medlineplus.gov/genetics/gene/stat3/

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#66

I still am trying to determine a dose here, but it is very unclear to me especially since I have no background in biochemistry. The total amount of IL-11 in a healthy control group is given at 44.51 pg/mL here (or 0.22255 µg in total for average person): https://journals.sagepub.com/doi/full/10.1177/17246008211023515, but in the only human clinical trial for anti IL-11 antibodies I could find the doses given were 300-600 mg.

The GPT-4o model gives for what the conversion should be at 1.757μg though. I can’t determine what a good source would be to even consider buying since they all appear to be distinct experimental compounds such as Anti-Human IL11 Antibody (SAA0379) and Research Grade Anti-Human IL11 Antibody (X203). Again from GPT-4o: " Different antibodies, even if they target the same antigen (IL-11), can have variations in:

  • Epitope specificity: Different antibodies may bind to different parts of the IL-11 molecule.
  • Conjugation tags: Some antibodies may be biotinylated, unconjugated, or conjugated with other tags for specific applications.
  • Isotype: The antibody’s class (e.g., IgG, IgM) can differ, affecting its binding and functional properties.
  • Application compatibility: Some antibodies are optimized for Western Blot (WB), Immunohistochemistry (IHC), Enzyme-Linked Immunosorbent Assay (ELISA), etc."
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#67

Interesting…

LASN01 had a half-life of >12 days in patients given a single dose of either 600 or 1200 mg and supports exploring monthly dosing in subsequent studies. A proprietary assay using ex-vivo stimulated whole blood showed >95% inhibition of IL-11R signaling by LASN01 with a single 300 mg dose or 600 mg dose that persisted for 4 and 8 weeks respectively. LASN01 is well tolerated, and robustly inhibits the IL-11 pathway in human volunteers.

The good news is that LASN01 is moving forward and may become a product commercially available, but I’m sure its going to be expensive:

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#68
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#69

There was an earlier thread on trametinib.

#70

According to Chat GPT-4o

Some natural compounds can influence inflammatory pathways and cytokines in general, which could have indirect effects on IL-11. Some examples:

  1. Curcumin

Evidence: Extensive research shows its ability to modulate various inflammatory pathways and cytokines, including IL-6 and others, suggesting an indirect effect on reducing IL-11.
Mechanism: Inhibits multiple inflammatory signaling pathways, including NF-kB.

  1. Quercetin

Evidence: Numerous studies highlight its anti-inflammatory capacity and impact on reducing pro-inflammatory cytokines.
Mechanism: Acts on various pathways, including the inhibition of cytokine production.

  1. Omega-3 Fatty Acids

Evidence: Well documented in the literature for their anti-inflammatory effects and regulation of cytokine production.
Mechanism: Modulate the inflammatory response, which may affect IL-11 production.

  1. Epigallocatechin Gallate (EGCG)

Evidence: Shown to have anti-inflammatory effects and can affect the production of various cytokines.
Mechanism: Acts as a potent antioxidant and influences cellular signaling.

Personally I would try Quercitin or Curcumin…

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#71

Sure.
The query I used with Dr. Oracle:
“Since blood tests for IL-11 are not commonly available, could the CRP blood test be used as a proxy to see if IL-11 is being suppressed?”

If you have a better query, I would be happy to try it.

Limitations of Using CRP as a Proxy for IL-11:

Different Roles and Pathways
CRP and IL-11 have distinct biological functions and signaling pathways.
CRP is primarily produced in the liver, while IL-11 is produced by various cell types, including synovial fibroblasts ([3]).

Lack of Direct Correlation
There is no direct evidence suggesting that CRP levels accurately reflect IL-11 suppression.
Studies have shown that IL-6, rather than IL-11, is more closely associated with CRP levels in inflammatory conditions ([3]

Multiple Influencing Factors
CRP levels can be influenced by various factors beyond IL-11 suppression, including:
Other inflammatory cytokines
Acute and chronic infections
Tissue damage
Cardiovascular events ([4])

Conclusion
While CRP is a valuable marker of inflammation, it cannot be reliably used as a direct proxy for IL-11 suppression. The relationship between these two markers is complex and influenced by multiple factors. Healthcare providers should consider the limitations of using CRP alone and may need to explore alternative or complementary approaches to assess IL-11 activity in clinical practice.

Role of C-Reactive Protein at Sites of Inflammation and Infection. (Frontiers in immunology, 2018)
C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. (Seminars in arthritis and rheumatism, 2021)
The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. (Arthritis and rheumatism, 1997)
C-reactive protein levels correlate with mortality and organ failure in critically ill patients. (Chest, 2003)
Evidence that C-reactive protein or IL-6 are not surrogates for all inflammatory cardiovascular risk factors in hemodialysis patients. (Blood purification, 2006)

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#72

I am a huge fan of Boswellia Serrata. Its effects are dose-dependent.
I am taking 2.4 grams (4 capsules) of Boswellia daily. At this dose, I am completely free of any NSAIDS or other painkillers. It is a powerful anti-inflammatory supplement and has reduced all joint pains to zero.

Boswellia serrata and IL-11 Suppression: A Potential Connection

Overview of Boswellia serrata’s Anti-inflammatory Properties

Boswellia serrata, a plant with known anti-inflammatory properties, has been the subject of several studies investigating its effects on the immune system. While there is no direct evidence of its impact on IL-11 specifically, research suggests that it may have broad anti-inflammatory effects that could potentially include IL-11 suppression.

Effects on Cytokines and Immune System

Cytokine Modulation

A study ([1]) found that Boswellia serrata extracts and boswellic acids can decrease several pro-inflammatory cytokines, including:

IL-1

IL-2

IL-4

IL-6

IFN-gamma

While IL-11 is not explicitly mentioned, this finding suggests that Boswellia serrata has the potential to suppress various inflammatory mediators.

Immune System Regulation

Research ([2]) indicates that Boswellia serrata extracts can influence regulatory and effector T-cell compartments, suggesting a potential for modulating immune dysregulation. This provides indirect support for the possibility that Boswellia serrata supplements might affect IL-11 levels.

Potential as an Alternative to NSAIDs

A comprehensive review ([3]) discusses the anti-inflammatory properties of Boswellia serrata and its potential as an alternative to NSAIDs. While this doesn’t directly address IL-11 suppression, it underscores the broad anti-inflammatory effects of Boswellia serrata.

Conclusion

While there is no direct evidence that Boswellia serrata supplements suppress IL-11, the available research suggests that it has broad anti-inflammatory effects and can modulate various cytokines and immune system components. The possibility of IL-11 suppression exists, but further research is needed to confirm this specific effect. The current evidence is indirect and based on Boswellia serrata’s known anti-inflammatory properties and its effects on other cytokines.

  1. Modulation of the immune system by Boswellia serrata extracts and boswellic acids. (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2010)
  2. Antioxidant and Ex Vivo Immune System Regulatory Properties of Boswellia serrata Extracts. (Oxidative medicine and cellular longevity, 2017)
  3. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. (Clinical pharmacokinetics, 2011)
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#73

@desertshores: would you care to ‘divulge’ the brand of Boswellia Serrata you are using. :slight_smile:

#74

This is geat news… I have been a big advocate of whole milk (1 to 2 glasses with meat protein) after my gym workout. Besides lots of milk. I daily consume cheeses… swiss and chedder… cheese curds when fresh and available.

Bovine lactoferrin (bLF), a naturally occurring glycoprotein found in milk, has bioactive characteristics against many microbes, viruses, and other pathogens.

Link: Evaluating the in vitro efficacy of bovine lactoferrin products against SARS-CoV-2 variants of concern - Journal of Dairy Science

Great news!

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20240626_2148271920×2560 617 KB

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#75

Sure:
Nutricost Boswellia Extract 65% Boswellic Acid Capsules (1,200 MG) (180 CAPS) - Gluten Free, Non-GMO, Vegetarian"

https://www.amazon.com/Nutricost-Boswellia-Boswellic-Capsules-Equivalent/dp/B0C4QD8YLQ/

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#76

I took that type for years and switched to an “ApresFlex” formulation (standardized for AKBA) since the bioavailability is better, so pills are smaller, and it’s been highly effective in studies. Do you have any thoughts on “ApresFlex”? Wondering if there are other important boswellic acids, aside from AKBA. I’ve been using this one: https://www.vitacost.com/vitacost-root2-boswellia-serrata-featuring-apresflex-100-mg-60-capsules

Thanks for the reminder about its potent anti-inflammatory effects. I think I’ll double up.

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#77

I have tried several different brands and they all have seemed effective.
Whenever I stop taking it my joint pains, especially my knees, start to return.

As I have said it is dose dependent. The capsules are very cheap as far as most supplements go. I just increase the dose until I find relief. This seems to take care of the bioavailability problem.

“Boswellia serrata, commonly known as Indian frankincense, has been used in traditional Ayurvedic medicine for centuries. The oleo gum-resin extracted from the Boswellia serrata tree has been employed to treat various chronic inflammatory conditions”

I don’t think they knew of the bioavailability problem.

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#78

I have a family member with chronic knee pain who lives with us and can’t swallow big pills, so switching to ApresFlex has allowed him to take it too.

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#79

This episode covers specialized pro-resolving mediators which are in drug development but are also built from EPA/DHA. Some fish oils like anchovoy oil also contain related omega 3s that act directly as resolvins. SPMs are molecules that can activate the natural resolution of inflammation and help people avoid anti-inflammatory drugs. The discovery of SPMs spurred a paradigm shift in our understanding of inflammation and human disease. Not the exactly the same as this topic but perhaps related

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#80

I was wondering if IL-11 might (partially) explain the success of plasma dilution therapy?
If there is “no downside” to reducing the amount of IL-11 circulating, then eliminating it from the blood would approximate an infusion of IL-11 antagonist or receptor blocker.
The unknown is the time taken for IL-11 to be replaced to previous levels. Hours? Days? Weeks? Months?

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#81

Wow, this story is really getting around, It even made the Boy Genius Reports…and with this little tidbit that will be of interest here…

The researchers also have to ensure that the anti-aging drug doesn’t completely eliminate inflammation, as a healthy amount is good for the body and helps you age normally. While we want to slow the aging process, we do not want to stop it altogether, as the body needs to age in order for it to work properly.

https://bgr.com/science/mice-lived-20-longer-after-astounding-anti-aging-drug-trial/

I’m struggling to understand how aging is helping my body to work properly.

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#82

I think it would be hard to do excessive anti-inflammation with simple over-the-counter anti-inflammatory supplements, excluding NSAIDs, if you only take the recommended doses. IMO: Anti-inflammatories are a key anti-aging factor.

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#83

IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR initiating a mesenchymal program in stromal, epithelial, and cancer cells

Anissa A. Widjaja,1,4,∗ Sivakumar Viswanathan,1,4 Joyce Goh Wei Ting,1,4 Jessie Tan,2 Shamini G. Shekeran,1 David Carling,3 Wei-Wen Lim,1,2 and Stuart A. Cook1,2,3,5,∗∗

Author information Article notes Copyright and License information PMC Disclaimer

Associated Data

Supplementary Materials

Data Availability Statement

Go to:

Summary

IL11 initiates fibroblast activation but also causes epithelial cell dysfunction. The mechanisms underlying these processes are not known. We report that IL11-stimulated ERK/P90RSK activity causes the phosphorylation of LKB1 at S325 and S428, leading to its inactivation. This inhibits AMPK and activates mTOR across cell types. In stromal cells, IL11-stimulated ERK activity inhibits LKB1/AMPK which is associated with mTOR activation, ⍺SMA expression, and myofibroblast transformation. In hepatocytes and epithelial cells, IL11/ERK activity inhibits LKB1/AMPK leading to mTOR activation, SNAI1 expression, and cell dysfunction. Across cells, IL11-induced phenotypes were inhibited by metformin stimulated AMPK activation. In mice, genetic or pharmacologic manipulation of IL11 activity revealed a critical role of IL11/ERK signaling for LKB1/AMPK inhibition and mTOR activation in fatty liver disease. These data identify the IL11/mTOR axis as a signaling commonality in stromal, epithelial, and cancer cells and reveal a shared IL11-driven mesenchymal program across cell types.

I hate to sound like a broken record but there is a simple intervention that powerfully activates AMPK , modulates mTOR, suppresses p16 and lowers resting IL-6 levels… couldn’t find much direct effect on IL-11.

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#84

Well, FWIW I agree with you. Inflammation is not only caused by IL-11 right? There are many other things.

There are people that don’t make the IL-11 and they do fine.

There are animals that don’t age much and they work properly. Such as it is. Lol.

He is getting the word out though, and fun to read.

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