IL1B

The IL1B gene codes for interleukin 1-beta (IL-1b). IL-1b is an important inflammatory immune messenger (cytokine). It’s released from white blood cells in response to cell stress, cell damage, or cell death, and can have an impact on metabolism and weight control. Variants of IL1B may play a role in chronic fatigue syndrome by changing energy production in the short and long term. They may also play a role in PTSD by stimulating the excess release of IL-1b. [R, R, R, R].

After its release, IL-1b acts as an “alarm bell,” signaling the release of many other pro-inflammatory compounds [R, R, R, R].

IL1B variants are linked to many conditions, including:

• Autoimmune disorders, such as rheumatoid arthritis and IBD [R, R]
• Inflammation of the pancreas (pancreatitis) [R]
• Cancer [R]
• Severe inflammatory response to infectious diseases [R]
• Heart disease [R, R]

Lifestyle, diet, and supplement modifications may counteract the effects of these variants by supporting healthy IL-1b function and promoting leptin sensitivity.

Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells.

The IL1B gene is responsible for producing interleukin 1-beta (IL-1β), one of the major types of pro-inflammatory cytokines [R, R, R].

Cytokines are one of the main types of “messenger” molecules that the immune system uses to regulate the inflammatory response. There are many different kinds of cytokines, each with their own unique functions and roles.

When it comes to members of the interleukin-1 family (which includes IL-1β), these compounds act as a sort of “alarm” signal that are produced (by dendritic cells, macrophages, monocytes, and neutrophils) in response to cell stress, damage, or death [R, R, R, R].

These “alarm signals” then trigger the production and release of many other pro-inflammatory compounds, such as [R, R, R, R, R]:

• Reactive oxygen species (ROS), the main causes of oxidative stress
• Nitric oxide
• NF-kB
• CREB
• STAT3

IL-1β further contributes to the inflammatory response by activating Th9 and Th17 cells, as well as stimulating the production of IL-6, another major pro-inflammatory cytokine [R].

In other words, nearly all cell types in the immune system either express or are targeted by cytokines in the IL-1 family [R]. For these reasons, cytokines in the IL-1 family — such as IL-1β — are primarily associated with both acute and chronic inflammation [R, R].

SNPs in the IL1B gene correlate with a range of inflammation-related disorders, such as:

• Autoimmune conditions (rheumatoid arthritis, IBD) [R, R]
• Pancreatitis (pancreas inflammation) [R]
• Cancer [R]
• Severe inflammatory response to infectious diseases [R]
• Heart disease [R, R]

IL1B and Chronic Fatigue Syndrome

The IL1B gene is responsible for producing interleukin 1-beta (IL-1b), one of the chief inflammatory cytokines. IL-1b acts as an "alarm signal" from white blood cells (macrophages, monocytes, and neutrophils) in response to cell stress or damage [R, R, R, R].

Although the release of IL-1b normally increases in response to infection, its release can also increase after exposure to psychological stressors. For example, researchers studying the effects of childhood trauma on healthy adults found a significant link between childhood trauma and increased blood levels of IL-1b [R, R, R, R].

IL-1b tends to be higher than normal in many psychological conditions, including PTSD [R].

However, in a meta-analysis of IL-1b levels in various diseases and disorders that cause fatigue, most studies found that IL-1b was lower than normal in patients with chronic fatigue syndrome (CFS) [R].

These results directly contradicted findings in mental illness and fatigue associated with stroke, cancer, or arthritis; in all of these cases, more fatigue was linked with higher IL-1b [R].

Some more detailed studies may help provide an explanation for this apparent conflict. One study found that short-term CFS patients had higher than normal IL-1b, while long-term CFS patients produced less IL-1b than expected. In another study, patients with moderate CFS had significantly higher IL-1b than patients with severe CFS [R].

In other words, IL-1b may increase with acute fatigue and decrease with chronic fatigue [R].

This complex relationship may have something to do with IL-1b’s role as a signal molecule in the brain, where it improves leptin signalling, reducing appetite and increasing fat-burning. Low IL-1b, as in the case of chronic fatigue patients, may reduce the brain’s sensitivity to leptin and decrease energy production from fat [R, R, R].

IL1B and PTSD

IL-1b is a protein (cytokine) released by cells of the immune system [R]. 

Although the release of IL-1b normally increases in response to infection, its release can also increase after exposure to psychological stressors. For example, researchers studying the effects of childhood trauma on healthy adults found a significant link between childhood trauma and increased blood levels of IL-1b [R, R, R, R].

Not surprisingly, IL-1b also plays a major role in the development of mental disorders, such as PTSD. Individuals with PTSD often experience symptoms of stress and anxiety in response to events that elicit traumatic, fear-based memories [R].

In PTSD, continuous exposure to elevated levels of IL-1b has been suggested to inhibit the growth of new brain cells (neurons) in a number of brain regions implicated in fear processing. This could alter the activity of these brain regions [R, R].

Variants of the IL1B gene have been linked to an increased risk of PTSD and its associated symptoms. These variants may stimulate the excess release of IL-1b in regions of the brain associated with PTSD, which could inhibit the growth of neurons in these brain regions and result in abnormal responses to fear-based memories [R, R, R].

Metabolic Health

Scientists have noticed that mice lacking the IL-1 family of cytokines are more prone to obesity. On the other hand, animals with enhanced IL-1 activity burn more fat, which makes them resistant to weight gain [R, R].

These findings seem contradictory, given that obesity is a pro-inflammatory state. Researchers dug deeper to reveal the exact mechanisms and suggested a surprising role of IL-1b in the brain: it appears to improve leptin signaling. Low IL-1b levels may contribute to leptin resistance [R, R].

Leptin is a crucial hormone that suppresses appetite and stimulates energy expenditure. Over-secretion leads to leptin resistance, a condition in which leptin loses the above functions [R].

Besides the central effect (in the brain), IL-1b may act directly on the fat tissue to release leptin and reduce the size of fat cells [R].

However, being an inflammatory cytokine, IL-1b has its dark metabolic side. It’s one of the primary cytokines involved in diabetes development. Patients with metabolic syndrome have elevated IL-1b, too [R, R].

Obesity and Fat Mass

One SNP in the IL1B gene, rs1143634, has shown a clear association with obesity and fat mass across different ages and ethnic groups.

Among 1,068 young Swedish men, those carrying the "GG" genotype had higher total fat mass and more fat in their arms, legs, and trunks. They also had slightly higher body mass index (BMI), likely due to differences in body fat [R].

In a trial of 880 older European (Caucasian) descendants, the "GG" genotype correlated with 34% higher rates of obesity [R].

Two studies of 438 Korean women observed up to five times lower frequency of the “A” allele among those who were overweight and obese [R, R].

Another IL1B SNP, rs1143627, showed a potential link with obesity. Among 3,014 Swedish elderly men, the “GG” genotype was associated with increased fat mass. However, other studies failed to confirm the association or yielded conflicting results [R, R, R].

Inflammation & Autoimmune Disorders

Different variants in the IL1B gene can influence how much IL-1β a person produces [R, R, R, R, R, R, R].

These differences, in turn, can influence how susceptible a person is to the effects of inflammation, and thus their likelihood of developing chronic inflammation and other associated health problems [R].

For example, SNPs in the IL1B gene have been associated with a variety of autoimmune and other inflammation-related disorders, such as:

• Rheumatoid arthritis [R, R]
• Pancreatitis (inflammation in the pancreas) [R]
• Autoinflammatory disorders, such as inflammatory bowel disease, Crohn’s disease, and ulcerative colitis [R, R]
• Severe inflammatory reactions due to common infectious diseases (such as the flu) [R]

However, the importance of IL-1β isn’t just limited to inflammatory disorders per se. This is because inflammation also contributes to the development of several other major types of health conditions, each of which can further impact lifespan.

Therefore, there are several additional major ways that genetic variations in IL1B may have an affect on overall lifespan, over and beyond the acute and chronic inflammation that IL-1β can contribute to.

Cardiovascular Health

Firstly, while acute inflammation is a normal part of the immune response, chronic inflammation can negatively impact the functioning of other organs and systems throughout the body.

One of the main systems affected by inflammation are the cardiovascular and circulatory systems. For this reason, chronic inflammation has been associated with the development of a number of significant cardiovascular health issues, including [R, R, R, R, R, R]:

• Atherosclerosis (hardening of the arteries)
• Coronary heart disease
• Myocardial infarction (commonly known as a “heart attack”)
• Heart failure
• Angina

Due to the link between elevated inflammation and long-term cardiovascular risk, certain genetic variants in the IL1B gene have been associated with the development of heart disease [R, R].

Furthermore, because cardiovascular disorders are a major cause of mortality, the link between chronic inflammation and heart disease forms another major pathway through which variants in the IL-1B gene can influence lifespan, over and beyond the “direct” effects of inflammation by itself.

Cancer Risk

Secondly, the other major way that IL1B may impact lifespan is by influencing a person’s long-term risk of developing cancer.

This is because — similar to cardiovascular health — evidence suggests that increased inflammation may be one potential causal factor in the development and growth of tumorous cells [R, R, R].

Although the link between inflammation and cancer is a general one, cytokines in the IL-1 family in particular have been associated with the early stages of cancer development and tumor growth. By extension, variants in the IL1B gene that increase the expression of IL-1β could increase a person’s long-term risk of developing cancer — which would have obvious negative effects on their likelihood of living long into older age [R].

Top Choices To Decrease IL-1beta

Top Functional Foods/Condiments

• Cod liver/Fish oil/DHA (R)
• Jasmine Tea/Tea Polyphenols (R)
• Kombucha/Lactic acid (R)
• Black Cumin Seed Oil (R)…not bad (R)
• Cinnamon/Sodium Benzoate (R)
• Raw honey (R)
• Stevia (R, R2)
• Golden berries (R)
• Trehalose (R, R2)

Top Devices and Lifestyle

• LLLT (R)
• Fasting (R) (Increases IL-1Ra)

Top Supplements to Inhibit IL-1b

• Andrographis (R) – Out of 20 plants, Andrographis inhibited IL-1b the most and was more potent than dexamethasone.
• PQQ (R)
• Fisetin (R)
• Gynostemma (R)
• Curcumin (R) – Powerful suppression in response to IMQ (R)
• Trans-Resveratrol 500mg +5g Leucine (R, R2)
• Luteolin (R)
• EGCG (R) – Powerful (R)
• Apigenin (R)
• Boswellia (R)
• Hydroxytyrosol (R) (not potent)
• Pterostilbene (R) (Strong…30uM)
• Reishi (R) – Powerful
• L Plantarum (R) – for the gut especially.

Foods To Decrease IL-1beta

In general, vegetables and fruit should help decrease IL-1b.

• Cyanidin-3-O-²-glucoside (C3G) – typical anthocyanin (R) – Found in many fruits.
• Ginger (R) – Has lectins, but was one of the most potent out of 20 medicinal plants (R).
• Sulforaphane/Broccoli sprouts/Cruciferous Vegetables (R).
• Anthocyanins (from red raspberries) (R)
• Oat polyphenols (R)
• Astaxanthin in fish (R)
• Betalain/Beets (R)

See More at: How To Perform Better And Be Healthier by Decreasing Interleukin-1 (IL-1b)