Inhibiting Interleukin-6 (IL-6): The Key To Health, Successful Aging and Vitality

Introduction to Interleukin-6

Fatores pró e anti-inflamatórios

Interleukin-6 (IL-6) is a cytokine with well-defined pro- and anti-inflammatory properties (R). It regulates the immune system and plays a role in cognitive function.  

IL-6 is elevated when you are sick and after exercise, especially aerobic exercise (R).

If exercise increases inflammatory markers, then why is exercise healthy? Well, when you exercise, your muscles release IL-6, which is anti-inflammatory. However, when your immune cells (macrophages) release it, it’s pro-inflammatory (R). The harmful effect has to do, in part, with it being released with other immune cells that synergize in a negative way.

IL-6 also suppresses Th1 cells, while it induces Th2 cells (R), so it’s worse for Th2 dominant folks. It also increases B cells, which is what produces antibodies and contributes to allergies and autoimmunity (R).

People who aren’t predisposed to autoimmune issues can also have elevated IL-6. It’s the cytokine that is involved in the diseases of modern civilization. The most common cause is probably obesity.

There are two ways that IL-6 can activate cells.  One way is anti-inflammatory and helps in tissue regeneration. Another is pro-inflammatory and causes all kinds of problems.  See below for a more detailed explanation.

The most common reasons for elevated IL-6 are obesity (R), chronic stress (R), too little sleep (R), eating too much – specifically, eating too much sugar or refined foods (R), smoking (R), excess alcohol, (R) and exercising too much (R) (more than 2 hours of intense exercise a day is probably not a good idea for most).

The Bad

IL-6 levels are increased in nearly all disease states (R).

It decreases Treg cells, which in turn blocks our ability to create tolerance for proteins we ingest – causing allergies (R).  It also increases the production of neutrophils, which is inflammatory (R).

Interleukin-6 is a decent predictor of cognitive decline in late midlife. A 10-year decline in reasoning was greater among people with high IL-6  than those with low IL-6. In addition, people with high IL-6 had 1.81 times greater odds of a decline in a test that measures normal cognitive function (R).

IL-6 may cause feelings of “hopelessness”. This state strongly correlated with IL-6 levels (R) and we know this cytokine can cause brain changes that lead to a worsened mood. IL-6 is also correlated with violent suicide, impulsivity, and monotony avoidance (R).

IL-6 causes elevated blood sugar levels, which we know is problematic for general health (R).

IL-6 levels are higher in people with IBS (R, R2).

Studies have found that IL-6 aggravates the effects of stress hormones (CRH) on our gut mucosa, which causes IBS (R). It also causes IBS by activating gut neurons (R), which alters peristalsis. IL-6 can cause leaky gut (R).

IL-6 may lessen fatigue by stimulating the HPA axis and suppressing TNF-alpha (thereby increasing orexin).  Specifically, it stimulates the release of the corticotrophin-releasing hormone (CRH) by the hypothalamus (reversed by a COX inhibitor) (R).

It increases nitric oxide (R), which can be good or bad, depending on the situation.

At higher levels, IL-6 increased the release of vasopressin and oxytocin (R), which acts to decrease urination, among other effects.

IL-6 suppresses or ‘hypermethylates’ gene expression in the brain, which leads to a variety of problems (R).

For example, it decreases BDNF, a brain growth factor, which is how it contributes to depression (R).

People with major depressive disorder have elevated IL-6 (TNF-alpha) (R) and it likely contributes to a worse mood overall.

It can also lead to lower testosterone levels (R).

While IL-6 decreases testosterone in normal cells, it increases production in prostate cancer cells, which is required for this cancer to grow (R). So it’s a double whammy – it decreases testosterone in normal cells and increases it in cancer cells. Damn you, IL-6!

IL-6 also decreases performance by decreasing the conversion of T4 to T3 (thyroid hormones), resulting in lower levels of T3.  This occurs as a result of IL-6 causing oxidative stress and lowering glutathione levels (R, R2).

IL-6 contributes to schizophrenia by inhibiting (or hypermethylation) a gene (GAD67) that is important for GABA to work properly (R).

HDAC inhibitors are beneficial for cognitive disorders because they increase gene expression for growth factors like BDNF. IL-6 does the opposite by increasing HDAC (R). Resistant starch is a powerful way to inhibit HDAC and therefore increase BDNF (R).

IL-6 is the most potent inducer of CRP, an inflammatory marker, but as I will explain below, you can have normal CRP levels and abnormal IL-6 levels.

It can create and worsen food sensitivities and autoimmune issues by increasing IgG and IgM antibodies (R). Testosterone decreases these antibodies, but IL-6 is capable of increasing them even with high levels of testosterone (R). (Estrogen increases these antibodies) (R).

IL-6 can also cause skin problems. When your natural skin fungus gets out of control the body attacks it with cytokines that include IL-6 (also IL-1b, TNF, IL-8), which recruits other aspects of the immune system (R). IL-6 is elevated in people with tinea versicolor, a skin fungus (R). IL-6 also increases Th22 cells, which disrupts skin microbial balance (R).

IL-6 (or IL-21 according to some) can increase Th17 cells, which are pro-inflammatory. To do this, you also need elevated TGF-β (R).

IL-6 can keep you from getting into ketosis. (R)

The Good

I would say IL-6 is mostly bad if elevated, but brief spikes can be beneficial, just like brief bouts of intense exercise.

TNF and IL-1b increase IL-6 (R), but IL-6, in turn, suppresses both of these cytokines, which are more harmful than IL-6 itself. In this way, it’s an anti-inflammatory (R).

IL-6 increases liver regeneration (R) and helps form emotional memories while sleeping (R).  

IL-6 Makes Us Thinner

It also inhibits TNF, breaks down fat cells and decreases insulin resistance (R).  

Science has discovered that exercise can help you lose weight more than by just burning calories; exercise changes your hypothalamus (R).

IL-6 is part of this mechanism by which exercise can help us lose weight (R).

IL-6 decreases insulin and leptin resistance in the hypothalamus, the gland that controls appetite (requires IL-10 to inhibit Nf-kB) (R).

IL-6 also increases spontaneous energy expenditure. Mice lacking IL-6 became obese. (R)

Figure 9<br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /><br /> Schematic diagrams of the proposed role of the hypothalamic anti-inflammatory response mediated by exercise.

IL-6 Can Fight Infections

IL-6 plays a protective role in many bacterial, viral, and fungal infections.

It has a protective role in the flu, H pylori, and EMCV (R). Mice deficient in IL-6 are significantly more susceptible to some fungal infections like candida (R).

In mice, IL-6 helps prevent common herpes infection (HSV-1), but it doesn’t prevent its reactivation (R).

Diseases Associated With Interleukin-6

IL-6 is responsible for causing many autoimmune diseases (R). There are many theories about how this occurs, but the point is that it’s causal and not just correlated. One way IL-6 does this is by decreasing the cells that regulate the immune system from attacking itself (Treg cells) (R).

If you decrease IL-6, you will decrease the progression of many inflammatory conditions.

This is a partial list:

Top Ways to Inhibit IL-6

Factors That Increase Interleukin-6


  • High blood sugar levels – High blood sugar levels activate immune cells like monocytes and increase inflammation (R).
  • PHA (lectin) (R), ConA (lectin) (R)
  • High glycemic index foods (R)
  • High-fat diet (R)
  • Coffee (R) – People who drank more than a cup had 50% greater IL-6 (association). Seems to be confirmed in a randomized control trial in people with diabetes, which showed a similar 60% increase (R).
  • Acrylamide (R) – found in  starchy foods such as potato chips (potato crisps), French fries, and bread that had been heated higher than 120°C (248°F) (production of acrylamide in the heating process was shown to be temperature-dependent). It was not found in food that had been boiled. Acrylamide is also found in black olives,  prunes, dried pears, coffee, cocoa powder and chocolate, formed during cacao bean roasting (R).


  • Chronic insomnia (R) – Elevates IL-6 in the day time.
  • Sleep deprivation (R)
  • Excessive exercise/Marathons (R)
  • Obesity (R)
  • Circadian Rhythm disruption (R)
  • Smoking (R)
  • Excess alcohol (R)
  • Chronic stress (R)
  • Viruses, like Herpes Virus (HHV8), can produce a protein similar to IL-6 that is even more inflammatory (R).
  • Infections (some). For example, people with lingering symptoms from Lyme have elevated IL-6 (R).




  • Aloe (R) – (in cancer cells)
  • 5-HTP (at lower and higher concentrations) (R)
  • Reishi (R)
  • Grapeseed extract (R) – in astrocytes, which is neuroprotective.
  • Astragalus (R)
  • Cat’s Claw (R)
  • Rooibos (R)
  • Grape powder (R) (LPS)
  • Creatine at very high dosages (R)
  • Phosphatidyl Choline— in response to infection (R)
  • Antidepressants: Imipramine and venlafaxine (at the higher concentration) (R). A combination of 5-HTP and fluoxetine (antidepressants) (both at the lower concentration) (R).

Interleukin-6 Inhibitors






Interleukin 6 on SelfDecode

What Are Healthy Interleukin-6 Blood Levels?

In healthy subjects, IL-6 blood levels are barely detectable and range between 2-6 pg/ml. Another study mentions that healthy people have a median level of 0.5 pg/ml (R). Depressed people had IL-6 levels about 1.78pg/ml greater than healthy people (R).

In people with Rheumatoid Arthritis, levels can increase up to a thousand-fold (not common).  In sepsis, which is extremely dangerous, it can increase up to a million-fold (R). (Sepsis is a potentially fatal whole-body inflammation caused by severe infection).

Chronically elevated levels will cause harm in the long run. One study checked for diseases of aging and IL-6 levels. After adjustment for potential confounders, they found that having a high interleukin-6 level (greater than 2.0 pg/ml) twice over a 5-year period nearly halved the odds of “successful aging” at the 10-year follow-up and increased the risk of future heart disease and overall death (R). (They only checked IL-6 levels twice).

Note that all of the people in the study were free of cancer and heart disease, so these weren’t what you’d call really sick people. They defined successful aging as “being free of major chronic disease and with optimal physical, mental, and cognitive functioning” (R).  I couldn’t define it better myself.

In people who exercised for 3-3.5 hours (marathon exercise), IL-6 increased from 1.5 pg/ml to 94.4 pg/ml immediately post-exercise and to 22.1 pg/ml 2 hours post-exercise (half-life of 1-2 hours) (R, R2). This means blood levels should be completely normal the next day – even after running a marathon.

In a group of people with cirrhosis, everyone with a proven bacterial infection had IL-6 levels above 200 pg/ml. On the other hand, 74% of the people with high IL-6 levels had these bacterial infections (R). These people had cirrhosis, so it would make sense that many would have high inflammation without bacterial infections. The takeaway is if you have high IL-6 levels without a chronic inflammatory condition, I would suspect some kind of infection.

In another study, patients hospitalized for moderate bacterial and viral infectious disease were checked for their cytokines. IL-6 was associated with a bacterial rather than a viral infection (R). This is useful information when trying to figure out if someone’s problems are more likely viral or bacterial. In the study, people who took antibiotics had their IL-6 normalize after only 3 days (from 39 to 2) (R, R2). The average IL-6 level for people with bacterial infections was 237 pg/ml. It was undetectable for viral infections (R).

I had a client check her IL-6 levels and her result was 528 pg/ml (see green arrows).

It happens that IL-6 is the main driver CRP, but CRP is not a reliable indicator, as you’ll read below. The client mentioned above had a high level of IL-6 at 528 pg/ml and her hs-CRP was 0.4, which is very low.

It should be noted that these numbers do not take into account the local IL-6 levels at the site of inflammation, which is largely unknown since they are mostly not experimentally accessible (R).

This can be the case where inflammation is more localized, so it won’t be picked up by these tests.  Therefore, not having elevated inflammatory cytokines isn’t definitive, but if you do have elevated cytokines, it’s certainly telling.

CRP Isn’t Such  A Reliable Factor

The most common way of checking inflammation – high-sensitivity C-reactive protein (hs-CRP) is not very relevant.

CRP is produced by the liver AND fat cells (R), so it makes sense that it’s more elevated in overweight people (R).

CRP is mainly increased by IL-6 (R), but also IL-1b and TNF.

IL-6 will be elevated moderately if you are overweight since IL-6 is also secreted by fat cells.

CRP will only show a spike, however, if you run marathons (maybe), have an acute infection, or incur a serious injury. These are situations where IL-6 spikes.

However, in most people with chronic inflammation who are thin, CRP will likely come back normal.

My CRP levels were low even when I was experiencing chronic, low-grade inflammation, and I didn’t experience fever.

To illustrate my point, many studies show IL-6 is elevated with IBS (R, R2). However, when a study checked for hs-CRP and IBS, the differences were significant but very small.

People with IBS have an average hs-CRP of 1.17, while healthy controls have a level of 0.72 (R). The standard value is under 3.0.

No doctor would even blink at the difference between 1.17 and 0.72.  They would tell you that you are perfectly healthy.

C-reactive protein correlated only weakly with interleukin-6 levels in people with cirrhosis (R).

Another example is cognitive decline. According to a study, elevated IL-6 but not CRP in midlife predicts cognitive decline (R). Obviously, these two inflammatory markers aren’t two peas in a pod.

In another example, although CRP levels were significantly lower in SLE than in Rheumatoid Arthritis, the concentrations of circulating TNF-alpha were higher in SLE (R).

I had a client with highly elevated IL-6 but at the same time a very low hs-CRP (0.4).

So we see from the IBS example that hs-CRP can tell us something, but we also see that in conditions with elevated IL-6, CRP can be more or less normal.

This is why we shouldn’t rely on hs-CRP as an indicator of inflammation and should take other tests.

IL-6: Pro and Anti-Inflammatory Effects

There are two types of IL-6. One is called “Classic signaling” and the other is called “Trans-signaling.”

IL-6 Classic signaling is needed for regenerative and anti-inflammatory roles.

IL-6 Trans-signaling takes place when IL-6 receptors (soluble IL-6 receptors or sIL-6R) in the blood bind with IL-6. This kind of cellular activation by IL-6 is what causes inflammatory problems (R).

In models of inflammation, autoimmune diseases, and inflammation-associated cancer, blockade of IL-6 trans-signaling was sufficient to block the inflammatory progress (R).

Fig 1

Fig 4

Disclaimer and Caveats


  1. JW

    Is this what causes encephalitis after getting sick or immunizarion – the immune system over reacts and turns on itself? The list above is extensive so are therre maybe a couple of really effective supps to take if this is a concern?

  2. Tommen

    Hi guys. I have been trying out burdock for the last months and it has had a great effect on my skin with regards to acne and inflamed hair follicles. Through selfdecode I have found out that I have most likely increased IL6 receptor proteins, and I just recently discovered that burdock is thought to inhibit IL6 in the skin and “detoxifying” the blood. On this basis, I believe the main factor for my bad skin throughout the years has been due to elevated IL6.

    I’m not that knowledgeable about inflammatory agents and the system around it, so I hope someone with this knowledge would be able to please give me advice on some of my queries?

    1. Would elevated IL6 in the skin signify that I have an elevated IL6 in my body, or is it possible that elevated IL6 may only be present in certain parts of my body?
    2. Do anyone know about any supplements that are powerful (or most powerful) in inhibiting IL6 in the brain, i.e. able to cross the blood brain barrier?


    • Tommen

      I am apparently blind to the information written on this page… however I hope my experience with burdock is useful for others in here.

      After further searching I found out luteolin and quercetin are good candidates for elevated IL6 in the brain.

      Although feel free to comment anything further related to my initial queries.

  3. paul

    My elevated cytokines:
    interleukin 1b – 993pg/ml (norm: 65-762)
    interleukin 6 – > 10000 pg/ml (norm: 2879-5956)
    interleukin 12 – 13 pg/ml (norm: 0-5,9)
    what can be the reason what these results and how to deal with them?

  4. Jon

    IL-6 + TGF-Beta = TH17 T Regulatory/Suppression – Not Inflammatories. IL-1B + IL-23 + RORgt, STAT3 = TH17 Inflammatory…. Just one pathway…. Coffee downregulates IL-1B and upregulates IL-6 – so coffee in the presence of high TGF Beta would result in TH17 Differentiation to Tregs…. Suppression of Inflammation…

    Or perhaps I am incorrect?

    Here’s a Question: How does Coffee affect IL-23???

    • Jon

      Both TH17 Inflammatory and TH17 T Regulators/Suppressors secrete IL-17 among other things. Just thought I would leave a comment here breifly while I am wrapped up in my search this afternoon for information on coffee and IL-23. 🙂

  5. Pete

    I forgot to say….I went into a depression after New Years, in which I spent a few days eating a lot of inflammatory foods, and I thought it was to do with the extreme winter we had. I booked a Caribbean cruise, and felt ok just before we left, and about two days into it, I felt horrible and down, which I attribute to overeating aboard the ship. It ruined my vacation. I would love to hear ideas regarding this.

  6. Pete

    I have had a serious dark cloud lift after being sick with a bad cold and taking antibiotics, I can’t do aerobic exercise without going through anxiety & depression, and when I eat too much or a lot of junk food, my eyes feel like they do when I’m under extreme stress, so after seeing this I am suspecting that this might be the cause.

  7. Sorry for spamming. I’m just on fire (thanks to the Acetaminophen).

    Ellagic acid penetrates the BBB. Might be really great for people with constant brain fog.

    Source 1:

    Yes, it seems to penetrate the human BBB as well.
    “Nevertheless, ellagic acid reduces significantly Aβ-induced neurotoxicity in human SH-SY5Y neuroblastoma cells. These results are in agreement with the hypothesis that Aβ fibril formation may represent a protective mechanism of local Aβ clearance. Thus, ellagic acid may have therapeutic value in Alzheimer’s disease.”

    Source 2:

    This seems like an interesting product. Probably has a high ellagic acid content:

  8. Also, what do you think about combining Lipoic Acid and Acetyl-L-Carnitine / L-Carnitine? Any experience with clients? We know that Lipoic Acid decreases IL-6 and Nf-Kb and Carnitine decreases both IL-6 and IL-1b. This could be a powerful combo.

    “Most notably, we found that when combined, LA and ALC worked at 100 to 1000 fold lower concentrations than they did individually. We also found that pretreatment with combined LA and ALC increased mitochondrial biogenesis and decreased production of reactive oxygen species through the upregulation of the peroxisome proliferator-activated receptor-gamma coactivator 1alpha as a possible underlying mechanism. This study provides important evidence that combining mitochondrial antioxidant/nutrients at optimal doses might be an effective and safe prevention strategy for PD.”

    However, this study was done using a cellular model.

  9. Btw. Astragalus definitely increases IL-6 (I noticed that you have listed it both as a “increaser” and “inhibitor”. I have been playing around with it for a good time now and I had to throw it away.

  10. L-Theanine for both IL-6 and IL-1b. Also works as a mast cell stabilizer and decreases histamine release. 1mg/kg rat dosage = 0.15mg/kg human dosage. We are talking about super low doses of theanine.

    “In our study, theanine 1 microM has a potent anti-inflammatory effect. We also found that anti-allergic effect of theanine 1 mg/kg was higher than that of dexamethasone at 5 mg/kg dose. Therefore, we can speculate that the activity found is at a dose that has meaning for actual clinical use. In conclusion, we showed that theanine inhibited mast cell mediated anaphylactic reactions. Theanine also inhibited TNF-a, IL-1b, IL-6, and IL-8 secretions and expression by blocking the activation of NF-jB and RIP-2/caspase-1. Our findings suggest that theanine has regulatory effects that may play a beneficial role in the treatment and management of allergic disorders.”

    Full study:

  11. Acetaminophen is the most potent IL-6 inhibitor I have tried. Instead of just taking my word for it I just found this study:
    “IL-6 increased with exercise in both groups (p<0.05) but the post-exercise response in the APAP was 55% lower (p<0.05) than the placebo group."

    Now, this is something! I have noticed that I have more mental clarity when I take it and I experience no pain in my muscles. My doctor prescribed me 665mg extended versions and I take two of them per day now (just to experiment).

    More interesting information:

    • PQQ doesn’t work for me at all when it comes to IL-6 inhibition. I even tried 60mg on an empty stomach and I didn’t notice anything. Same thing with quercetin on higher doses >1000mg. Are you really sure that these deserve a spot in the “Top way to inhibit IL-6” ? 🙂

    • Kat

      Hi Jean, I am interested in getting in touch with you if it is at all possible.
      One thing is I would like to get some tips on your research tactics since I am trying to do a lot of it myself. Thank you!

  12. I have tried extended release nicotinamide (1500mg, 8 hours) for a couple of days now and I have to say that it is absolutely amazing. Zero brain fog, lots of energy and I am feeling again – not as numb as I usually am. Better than modafinil, ritalin, coffee, etc. in terms of concentration, wakefulness and energy in my personal opinion. I am aware of the risks of hepatotoxicity and I think that it could be dangerous in a fasted state or in ketosis. But by eating 3-4 big meals I don’t think that there are any risks. I know how it feels when my liver is being damaged. I always get this warm weird feeling in my stomach, but with this I haven’t experienced anything yet. “NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1β or IL-8 expressionNCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1β or IL-8 expression” Source:

    The article below actually gave me the idea to try it. This amazing feeling I’ve been experiencing was a nice side benefit.

    • Joseph M. Cohen

      Thanks! Keep in mind that the 1% diet didn’t increase IL-6… This means that commonly supplemented levels are unlikely to increase IL-6. My guess is you are having negative effects because of a dif reason.

    • Joseph M. Cohen

      Thanks! Doesn’t contrast. They are in different cell types. All of the herbs you see that increase IL-6, my bet is they decrease it under other conditions or cell types. I just didn’t have the references.

  13. Jiri

    Absolutely incredible work Joe…you are my hero! Everybody who study immunity must READ your posts…keep us well informed please!

  14. abraham weiss

    Hi, I appreciate your posts tremendously; I believe there is nothing alike!
    Please keep up with your wonderful work.

    Thank You.

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