#1

Thought this deserves a thread all of its own.

I asked ChatGPT:

what are the top 40 inflammation reducing drugs and their cytokine target?

ChatGPT responded:

Here’s a comprehensive list of 40 inflammation-reducing drugs along with their primary cytokine targets where applicable. These drugs target various cytokines involved in inflammatory processes:

  1. Adalimumab (Humira) - TNF-alpha inhibitor
  2. Infliximab (Remicade) - TNF-alpha inhibitor
  3. Etanercept (Enbrel) - TNF-alpha inhibitor
  4. Certolizumab pegol (Cimzia) - TNF-alpha inhibitor
  5. Golimumab (Simponi) - TNF-alpha inhibitor
  6. Anakinra (Kineret) - IL-1 receptor antagonist
  7. Canakinumab (Ilaris) - IL-1β inhibitor
  8. Rilonacept (Arcalyst) - IL-1 inhibitor (IL-1α and IL-1β)
  9. Tocilizumab (Actemra) - IL-6 receptor inhibitor
  10. Sarilumab (Kevzara) - IL-6 receptor inhibitor
  11. Sirukumab (no longer marketed) - IL-6 inhibitor
  12. Secukinumab (Cosentyx) - IL-17A inhibitor
  13. Ixekizumab (Taltz) - IL-17A inhibitor
  14. Brodalumab (Siliq) - IL-17 receptor inhibitor
  15. Ustekinumab (Stelara) - IL-12/IL-23 inhibitor
  16. Risankizumab (Skyrizi) - IL-23 inhibitor
  17. Guselkumab (Tremfya) - IL-23 inhibitor
  18. Abatacept (Orencia) - T cell co-stimulation blocker (inhibits IL-2)
  19. Methotrexate - Folate antagonist (exact cytokine target varies)
  20. Leflunomide (Arava) - Pyrimidine synthesis inhibitor (exact cytokine target varies)
  21. Sulfasalazine - NF-kB inhibitor (exact cytokine target varies)
  22. Hydroxychloroquine - Antimalarial (exact cytokine target varies)
  23. Colchicine - Inhibits microtubule polymerization (exact cytokine target varies)
  24. Prednisone - Glucocorticoid (broad anti-inflammatory effects)
  25. Dexamethasone - Glucocorticoid (broad anti-inflammatory effects)
  26. Budesonide - Glucocorticoid (broad anti-inflammatory effects)
  27. Tacrolimus (Prograf) - Calcineurin inhibitor (inhibits IL-2)
  28. Cyclosporine (Neoral) - Calcineurin inhibitor (inhibits IL-2)
  29. Azathioprine (Imuran) - Purine synthesis inhibitor (exact cytokine target varies)
  30. Mycofenolate mofetil (CellCept) - Inosine monophosphate dehydrogenase inhibitor (exact cytokine target varies)
  31. Apremilast (Otezla) - Phosphodiesterase-4 inhibitor (regulates multiple cytokines)
  32. Janus Kinase (JAK) Inhibitors:
  • Tofacitinib (Xeljanz) - JAK1 and JAK3 inhibitor
  • Baricitinib (Olumiant) - JAK1 and JAK2 inhibitor
  • Upadacitinib (Rinvoq) - JAK1 inhibitor
  1. Dupilumab (Dupixent) - IL-4 and IL-13 inhibitor
  2. Benralizumab (Fasenra) - IL-5 receptor antagonist
  3. Mepolizumab (Nucala) - IL-5 inhibitor
  4. Reslizumab (Cinqair) - IL-5 inhibitor
  5. Omalizumab (Xolair) - IgE antibody (modulates allergic response)
  6. Belimumab (Benlysta) - BLyS-specific inhibitor (modulates B cell activation)
  7. Etokimab (not widely approved) - IL-33 inhibitor
  8. Rituximab (Rituxan) - CD20 antibody (targets B cells, which can produce inflammatory cytokines)

These drugs are utilized in various autoimmune diseases, inflammatory conditions, and allergic disorders. They work by modulating specific cytokines, receptors, or cellular pathways involved in the inflammatory response, thereby reducing inflammation and associated symptoms.

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Inflammaging Is Chronic, Stealthy and Can Be a Serious Threat to Your Health (WSJ)
Study - Inhibition of IL-11 Signaling Extends Mamillian Lifespan and Healthspan
#2

What drugs inhibit Interleukin 11 in humans?

ChatGPT response:

As of my last update in January 2022, there are no specific drugs approved for the direct inhibition of interleukin-11 (IL-11) in humans. IL-11 is a cytokine that plays a role in various biological processes, including inflammation and hematopoiesis. While several drugs indirectly affect IL-11 levels by modulating broader inflammatory pathways or cytokine networks, there are no medications specifically designed to target IL-11 alone.

Research into IL-11’s role in diseases such as cancer and inflammatory disorders is ongoing, and future drug development efforts may lead to therapies that directly target IL-11 or its receptors. For now, treatments for conditions where IL-11 may be implicated typically involve broader immunomodulatory or anti-inflammatory approaches rather than specific IL-11 inhibitors.

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#3

Related to this topic of inflammation drugs, I’ve been rather positive on colchicine lately, since this research came out: Gout Medication Colchicine Reduce Myocardial Infarction? 2019 N Engl Journal

But, I recently entered colchicine into my “MyRxProfile” app: Tracking Medication Risks and Interactions - Myrxprofile App

It highlighted two “Major” warnings, as outlined below. So, no plans for colchicine now. I don’t typically use grapefruit juice or grapefruit, so its less of an issue, but given that high doses of colchicine can be fatal, its a warning I take extremely seriously.

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#4

Thank you for that. I use GFJ extensively and I don’t want anything that can be fatal. I’ll pass on this one. There’s too many other better options out there!

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#5

Based on my results, I am on a mini-crusade to get people to at least try
Boswellia Serrata for its anti-inflammatory properties.
Other than subjective results you could measure your CRP before and after taking the supplement for sometime.

Dr. Oracle: Boswellia Serrata as an Anti-inflammatory

“In conclusion, Boswellia serrata and its standardized extracts show significant potential as anti-inflammatory agents, particularly in the management of osteoarthritis and rheumatoid arthritis”

Mechanism of Action
Boswellia serrata, commonly known as Indian frankincense, has demonstrated significant anti-inflammatory properties. Its primary mechanism of action involves:

Inhibition of pro-inflammatory enzymes, particularly 5-lipoxygenase (5-LOX) ([1])
Suppression of inflammatory mediators such as TNF-α, IL-6, and IL-1β ([1])
Modulation of the NF-κB signaling pathway ([2])
Efficacy in Inflammatory Conditions
Osteoarthritis
Boswellia serrata extract has shown promising results in managing osteoarthritis:

Reduction in pain and stiffness ([3])
Improvement in physical function ([3])
Decrease in inflammatory markers such as high-sensitive C-reactive protein ([4])
Rheumatoid Arthritis
Studies have demonstrated the potential of Boswellia serrata in rheumatoid arthritis:

Attenuation of inflammatory mediators and oxidative stress ([1])
Modulation of the immune system ([1])
Standardized Extracts
Several standardized extracts of Boswellia serrata have been developed and studied:

Aflapin (AprèsFlex)
Standardized to 20% 3-O-acetyl-11-keto-β-boswellic acid ([4])
Shown to be fast-acting and effective in managing osteoarthritis symptoms ([4])
5-Loxin®
Contains not less than 30% 3-acetyl-11-keto-β-boswellic acid ([2])
Demonstrated efficacy in reducing joint pain and cartilage degeneration in animal models ([5])
Dosage and Administration
Typical dosages range from 100-200 mg daily ([4])
Treatment duration of at least 30 days is recommended for significant improvements ([4])
Safety Profile
Boswellia serrata extracts have generally been found to be safe and well-tolerated:

No significant adverse effects reported in clinical trials ([4])
Long-term studies (up to 120 days) have confirmed safety ([6])
Caveats and Considerations
While promising, more large-scale, long-term clinical trials are needed to establish definitive efficacy ([7])
Individual responses may vary, and it’s essential to consult with a healthcare provider before initiating treatment
Potential interactions with other medications should be considered
In conclusion, Boswellia serrata and its standardized extracts show significant potential as anti-inflammatory agents, particularly in the management of osteoarthritis and rheumatoid arthritis. Their multi-faceted mechanism of action, coupled with a favorable safety profile, makes them an attractive option for healthcare providers considering alternative or complementary treatments for inflammatory conditions.

:speech_balloon: Ask a follow-up question here. Topic will be limited to the above discussion.

References

Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis. (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2014)
Extract Containing 30% 3-Acetyl-11-Keto-Boswellic Acid Attenuates Inflammatory Mediators and Preserves Extracellular Matrix in Collagen-Induced Arthritis. (Frontiers in physiology, 2021)
Efficacy evaluation of standardized Boswellia serrata extract (Aflapin) in osteoarthritis: A systematic review and sub-group meta-analysis study. (Explore (New York, N.Y.), 2024)
Efficacy and Safety of Aflapin®, a Novel Extract, in the Treatment of Osteoarthritis of the Knee: A Short-Term 30-Day Randomized, Double-Blind, Placebo-Controlled Clinical Study. (Journal of the American Nutrition Association, 2023)
Extract, 5-Loxin®, Prevents Joint Pain and Cartilage Degeneration in a Rat Model of Osteoarthritis through Inhibition of Inflammatory Responses and Restoration of Matrix Homeostasis. (Evidence-based complementary and alternative medicine : eCAM, 2022)
A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. (Phytotherapy research : PTR, 2019)
Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. (BMC complementary medicine and therapies, 2020)

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#6

I ordered and started today - thank you ! I’ll definitely comment on any results - my knees will tell me loud and clear.

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#7

Case study of long term usage of low dose prednisone as an anti-inflammatory agent: My mother had polymyalgia rheumatica in her mid life so she was on 20mg Prednisone for 2 years and an very effective agent and dose. Eventually she stayed on for more than 20+ years on and off at low dose of 2.5 to 5mg for RH. Amazingly, it did not affect her bone density (good to begain with). She took little other anti-inflammatory medications.

The point of the case is that low dose intermittent Prednisone (2.5mg) may not a terrible thing for older people who has inflammation issues if they do not have the access or indication for all those very expensive biologics.

However, I talked to many doctors about this, everyone of them is strongly against the idea. But what’s the alternative if you are not on biologics and have low to mid level inflammation? Diet and Lifestyle of course are a given.

I have talked many rheumatologists over the years and learned two things:

  1. the only thing in rheumatology certain is “uncertainty” (diagnosis).
  2. treatments are all the same or similar under the big umbrella.

I am making a point that perhaps a low dose anti-inflammatory agent intermittently is not a bad thing for longevity practice. The Q is which one to use?

#8

@RapAdmin Any medication on the long list potentially downgrade IL-11 pathway and signal?

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#9

Bazedoxifene

Bazedoxifene, a selective estrogen receptor modulator (SERM), has shown promise in inhibiting IL-11 signaling:

  • It blocks the formation of the IL-11:IL11Rα:gp130 signaling complex
  • Suppresses IL-11-mediated STAT3 activation in a dose-dependent manner
  • Has demonstrated efficacy in preclinical models of gastric and colon cancers

Bazedoxifene’s ability to disrupt IL-11 signaling, combined with its existing FDA approval for other indications, makes it a strong candidate for repurposing.

JAK Inhibitors

Since IL-11 signaling activates the JAK/STAT pathway, existing JAK inhibitors could potentially be repurposed:

  • Drugs like tofacitinib, baricitinib, or ruxolitinib may interfere with IL-11 signaling
  • These medications are already approved for various inflammatory conditions

Anti-IL-11 Antibodies

While not a repurposed medication per se, neutralizing antibodies against IL-11 or IL-11Rα have shown promise in preclinical studies:

  • In vitro experiments with IL-11-neutralizing antibodies yielded promising results in breast cancer cells
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#10

A regular nonsteroidal anti-inflammatory drug can also reduce inflammation. Maybe take it once or twice a week. For example, acetylsalicylic acid, diclofenac, etc.

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#11

And now for something completely different. Tart cherry juice reduces LDL and hsCRP.

I love tart cherry juice, so I’m going to try it out!

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