Interleukin-6: The Inflammation Marker You Need to Know

By now, most people have learned that surviving COVID-19 often comes down to having a well-performing immune system and low levels of chronic inflammation. But how do you know if your immune system is in good shape?

Promising new research shows that interleukin levels might be one of the strongest predictors of future health outcomes, including for COVID-19 patients. Unfortunately, the general public (and many health care professionals) aren’t aware of the importance of dysregulated interleukins.

This article aims to lay out a simplified explanation of what interleukin-6 does – and what factors can help reduce high levels of interleukin-6 in the body.

Do I Have a Dysfunctional Immune System?

There are three ways to get an indication of having a higher-than-average immune risk:

1. If you are older and have underlying health issues (e.g. diabetes, high blood pressure, severe arthritis, cancer, dementia), or your immune system is compromised by stress, poor sleep, or malnourishment.

2. If you frequently use antibiotics, cortisone, or are undergoing cancer treatment.

3. If your blood samples show increased sedimentation rates, abnormal blood cells, or dysregulated interleukins.

These factors are especially good to be aware of since – in today’s COVID-19 era – some epidemiologists think that one of the best public health strategies may be to identify people at increased risk of infection complications and shelter them from bacterial or viral exposure (1).

What Are Interleukins?

Interleukins are cell proteins that are heavily involved in controlling our immune system and ensuring that it’s responsive to invading microbes. Having too many – or too few – of these interleukins is equally bad and puts us at risk. These immune system markers can be measured (typically through blood or saliva tests) in order to get a better indication of our bodies’ readiness to respond to infections and diseases.

While there are many different interleukins, let’s focus on interleukin-6 (IL-6), which has been heavily researched since its discovery over 30 years ago.

Health problems arise when your interleukin-6 levels are chronically out of balance. In most cases, this means an overproduction of IL-6.

What Does Interleukin-6 Do?

IL-6 has been described as a sort of “Dr. Jekyll and Mr. Hyde” molecule, with both pro-inflammatory and anti-inflammatory functions (2).

Because of its dual role in the body, some conditions – like immunodeficiency – are characterized by too low levels of IL-6 (3). In the majority of cases, however, people suffer from having too high levels.

High IL-6 is strongly associated with chronic inflammation and most pro-inflammatory diseases, including obesity, arthritis, cancers, and much more. For this reason, IL-6 is typically used as an inflammation marker in research studies (4). While IL-6 will not give you a specific diagnosis of what’s wrong, you can think of it as an alarm bell.

A Predictor of Early Death

High IL-6 levels are also a strong predictor of all-cause early mortality in older adults (2, 4). Particularly, if a patient’s IL-6 levels do not go down during treatment for cancer or severe infections, it is an ominous sign as to the patient’s outcome (2).

This pattern holds true for COVID-19 patients as well. Patients who were classified as “critically ill” with COVID-19 had higher IL-6 levels at the start of their illness, and their levels continued to rise (rather than decrease) despite treatment (5).

How IL-6 Influences the Microbiome

IL-6 is involved in many aspects of our immune system, including modulating the balance of our gut bacteria. When levels are high, it indicates that the integrity of the intestinal wall may be in jeopardy. That’s because IL- 6 increases intestinal leakage (also known as ‘leaky gut’), which allows bad bacteria or viruses to enter our bodies (6, 7).

Microbiome health also has a profound effect on IL-6: “Bad” endotoxin-producing bacteria stimulate Il-6 production (8).

As we have written about before, microbiome imbalances may be the main driver of chronic inflammation and a dysregulated immune system. Since IL-6 has a strong influence on the microbiome, it’s not strange that IL-6 is a crucial player in health and disease.

Even if you have chronic inflammation issues and high levels of interleukin-6, there are numerous evidence-based ways to bring those levels down. 

8 Ways to Help Decrease Interleukin-6 Levels

As mentioned above, almost all pro-inflammatory conditions are characterized by increased IL-6. So is there a notable way to reduce interleukin-6 levels?

Certain medical drugs can help for specific conditions like rheumatoid arthritis. However, many common wellness strategies can also make a significant difference. Below are some of the best researched strategies known at this time:

1. Getting Good Quality Sleep

It’s no surprise that getting a good night’s rest is important for maintaining normal IL-6 levels. A meta-analysis of 72 studies found that sleep disturbances were associated with higher IL-6 levels (9). Why? For one, sleeping poorly is typically related with lower melatonin production.

A sizable body of research has separately documented that melatonin supplementation can reduce IL-6 (likely because of melatonin’s anti-inflammatory effect) (10, 11, 12, 13). Indeed, some researchers found that IL-6 levels dropped with as much as 34% after high dose melatonin supplementation (14).

2. Eating a Nutrient-Dense Diet

Eating fast foods made with processed ingredients and loaded with sugar is associated with high IL-6 (15). On the other hand, studies show that people who adhere to a Mediterranean diet – rich in fibers and polyphenols from nuts, legumes, fruits and vegetables – typically have lower IL-6 levels (16).

Consuming enough probiotics also seems to have a significant beneficial effect (4). The same goes for eating more seafood (15).

Eating a Mediterranean Diet – filled with foods rich in fibers, probiotics, polyphenols (antioxidants) and omega-3s – is a great way to reduce IL-6 levels.

3. Getting Enough Vitamin D

The research surrounding vitamin D and IL-6 is not always straightforward. Some meta-analyses have found that vitamin D3 supplementation significantly reduced IL-6 levels (17), while others did not find a similarly significant effect (4).

One thing we do know, however, is that a vitamin D deficiency is associated with increased IL-6 for numerous conditions, so there does seem to be a connection between vitamin D and inflammation (18, 19).

4. Practicing Good Oral Health

Oral hygiene doesn’t often make the typical list of lifestyle recommendations, but there’s good reason to consider it: The mouth is one of the key entry points in the body for bacteria, and therefore, plays a surprising role in the development of disease (20).

Higher IL-6 levels are typically documented in patients with oral health issues like periodontitis, gingivitis, and cavities (even in young children) (21, 22). To date, studies have found that practicing good oral hygiene can help lower the levels of IL-6 again (22).

While IL-6 levels typically spike immediately after exercise, studies show that being active regularly can help decrease IL-6 over time. 

5. Moderate Exercise

It’s important for the body to generate enough IL-6 for the right occasions. After exercise, for instance, the body typically produces more IL-6 to help maintain energy and repair any skeletal muscle damage. This is generally a positive thing (23).

The key thing to remember is that, while acute spikes in IL-6 is normal, having chronically high levels becomes problematic. Research shows that those who are less physically active have higher IL-6 levels than disciplined exercisers (16). In addition, researchers have also found that regular exercise, combined with eating a low calorie diet, significantly decreases IL-6 levels (16).

6. Maintaining Normal Body Weight

Obesity is not only associated with chronic, low-grade inflammation – it also seems to fuel it. Our fat tissue increases the production of IL-6, as well as other pro-inflammatory cytokines (24). Conversely, anorexia and other eating disorders are also associated with increased IL-6 levels, so it’s vital to have a healthy approach to weight management (25).

7. Reducing Stress

Stress triggers the release of proinflammatory cytokines (26), so it’s not surprising that people who regularly experience anxiety, fear – or even anger – tend to have higher IL-6 levels (27, 28). These levels also seem to be heightened in people who face regular stressors such as discrimination, and in those who have experienced childhood abuse (29, 30).

While the stressors in our lives are not always within our control, research indicates that there are ways to mitigate the damage. For instance, one study of breast cancer survivors demonstrated that practicing a type of mindfulness therapy (MBSR) helped reduce IL-6 levels (31). That is especially encouraging, since breast cancer survivors frequently continue to struggle with stress and anxiety symptoms after traditional cancer treatment.

When it comes to omega-3s, getting an effective dose matters. Studies show most people need at least 2000 mg of EPA/DHA daily to see an effect on pro-inflammatory markers – and possibly more for obese individuals.

8. Getting Enough Omega-3s

As mentioned above, eating more seafood is associated with lower IL-6 levels. In addition, numerous studies and meta-analyses show that taking omega-3 supplements consistently helps reduce IL-6 levels too. Consider one 2018 study, which found that over the course of 8 weeks, a daily dose of 2500 mg of EPA/DHA reduced IL-6 levels by 22% (32).

Omega-3 supplementation appears to be so effective for reducing IL-6 (and other pro-inflammatory markers) that three recent systematic reviews called it “one of the most promising treatments targeting inflammation in older adults” (4).

Getting an effective omega-3 dose, however, makes a crucial difference. Studies have found that people typically need more than 2000 mg of EPA/DHA per day to reduce the production of proinflammatory interleukins, like IL-6. In addition, higher EPA+DHA doses may be necessary to ultimately reduce levels of proinflammatory interleukins in obese individuals (compared to non-obese individuals) (32).

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