IL10

The IL10 gene codes for interleukin-10 (also abbreviated as IL-10), a cytokine with a complex relationship with inflammation. In fact, most of the time, IL-10 is anti-inflammatory and suppresses the activity of Th1 cells, Th2 cells, neutrophils, macrophages, and natural killer cells. Variants of IL10 may play a role in lupus by disrupting B cell function and decreasing total circulating IL-10. [R, R, R].

Lifestyle, diet, and supplement modifications may counteract the effects of these variants by supporting normal IL-10 function.

Some of IL-10’s functions include:

• Decreasing the activity of white blood cells [R]
• Decreasing inflammatory cytokine activity [R]
• Maintaining heart & blood vessel health [R]
• Blocking pain signals [R]
• Blocking allergic reactions [R]
• Increasing insulin and leptin sensitivity [R]
• Increasing regulatory T cell (Treg) activity [R]

Imbalance in IL-10 levels may contribute to:

• IBS [R, R]
• Depression [R]
• Anxiety [R, R]
• Autoimmune disease [R, R, R, R]
• Asthma and allergies [R]
• Sleep apnea [R]
• Developmental disorders [R]
• Psoriasis & eczema [R, R]
• COPD [R]

Variants in the IL10 gene have further been linked to [R, R, R]:

• Behcet’s disease
• Ulcerative colitis
• Severity of HIV/AIDS

Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells.

The IL-10 protein has many functions that all center around the immune system and inflammation [R].

Generally speaking, IL-10 helps suppress compounds that cause inflammation while stimulating certain components of the immune system [R].

Some of the functions of IL-10 include [R, R]:

• Blocking inflammatory cytokines, such as TNFα, IL-1β, and IFNγ
• Stimulating the development of T cells, B cells, and antibodies
• Blocking the activity of NF-κB

The IL-10 protein primarily works by limiting the body’s immune response to pathogens. A pathogen is any infectious agent that can cause disease, such as bacteria, viruses, and fungi [R, R].

IL-10 primarily does this by blocking the immune system’s ability to recognize pathogens. This prevents the body from triggering an inflammatory response [R, R].

However, this activity is not always beneficial. Excessively blocking the body’s ability to recognize pathogens can increase the risk of infection [R, R].

Research shows that certain variations in the IL10 gene may predispose individuals to several health conditions, including autoimmune disorders, inflammatory diseases, and infections [R, R, R].

More intriguing, perhaps, are the studies that have found that certain variants of IL10 may be associated with longer lifespans [R, R].

Lupus

IL-10 has a complex relationship with autoimmunity. On the one hand, IL-10 suppresses the activity of almost all other white blood cells [R, R, R].

On the other hand, this cytokine stimulates the production of antibodies from B cells; if the antibodies being produced attack the body’s own tissues, then an autoimmune reaction may result. Indeed, one study found that lupus patients with high IL-10 were significantly more likely to develop severe forms of the disease [R, R].

But that’s not where the complications end: a Japanese study found that people with lupus were likely to have autoantibodies that bind to IL-10. The authors suggested that IL-10 antibodies could be causing abnormal B cell activity in lupus patients [R].

The final point of complexity comes from variants in the IL10 gene. The alleles associated with increased lupus risk are also associated with decreased IL-10 levels [R, R].

Intestinal Tract

IL-10 also helps control the inflammatory response in the digestive tract. Specifically, it reins in our immune system in the gut, preventing it from attacking the beneficial bacteria that live there and help digest our food [R, R, R].

In both animals and humans, mutations in the IL10 gene have been associated with intestinal inflammation. Children with mutations that cause IL-10 deficiency may develop severe, therapy-resistant enterocolitis [R, R, R].

Variants in IL10 that reduce IL-10 production have also been associated with IBS, ulcerative colitis, and Crohn’s disease [R, R, R].

IL-10 is generally an anti-inflammatory marker, meaning that high IL-10 is generally associated with lower rates of inflammatory diseases like IBS and IBD [R, R, R].

Two well-studied IL10 variants have been associated with either IBS or IBD. At the first, rs1800896, the minor ‘C’ allele is associated with increased IL-10 production and lower rates of irritable bowel syndrome (IBS) [R, R, R, R, R].

At the second, rs3024505, the minor ‘A’ allele is associated with decreased IL-10 and higher rates of IBD (both ulcerative colitis and Crohn’s disease) [R, R].

Lifespan and Longevity

There is evidence that the IL10 gene has a significant impact on lifespan. More specifically, variants of IL10 that increase the production of IL-10 may be associated with better longevity [R].

How does increasing the production of IL-10 improve longevity?

According to some researchers, one possible explanation may be the anti-inflammatory effects of IL-10. Increased IL-10 levels may help prevent inflammation-related diseases, which may improve overall survival [R].

Another possible mechanism is the effect of IL-10 on cancer. According to animal studies, increased production of IL-10 may help inhibit tumor growth and suppress the ability of cancers to spread [R, R].

However, there are still some questions regarding the benefits of increased IL-10 production. For example, high levels of IL-10 can also increase the body’s susceptibility to infections, which would negatively affect longevity [R, R].

Research suggests that the IL10 gene may play a role in longevity. The ‘CC’ genotype in rs1800896 (sometimes called IL-10 -1082) appears to be associated with longer lifespans [R, R].

One study looked at the genetic information of 450 Italian men and women. Researchers found that the ‘CC’ genotype was significantly more common in men who were 100 years or older [R].

However, this association between the ‘CC’ genotype and longevity was not present in women [R].

A follow-up study of 401 men and women (also from Italian populations) revealed similar results. The ‘CC’ genotype was much more common in men who lived exceptionally long lives, but there appears to be no effect in women [R].

Not all studies have found evidence that the IL10 gene influences longevity.

For example, several studies have shown no link between rs1800896 and longer lifespans. This includes research that has examined Finnish, Irish, and Sardinian populations [R, R, R].

On top of that, one study suggests that the ‘T’ allele (rather than the ‘C’ allele) may be more common in those that have longer lifespans, based on data taken from a Jordanian population [R].

If you have low producing IL-10 genes, then you want to increase IL-10.

How to Increase IL-10

Lifestyle

• Calorie Restriction (R)
• Sun/UVB light (R),
• Exercise (R) – IL-10 showed a 27-fold increase immediately post exercise. (R)
• Wim Hof Breathing/Meditation (R)

Diet

• Sesame oil (R)
• Cinnamon/NaB (R),
• Garlic (R),
• Cayenne/Capsicum (R),
• Licorice (R)
• Butyrate/Hi-maize (R) – humans.  only smaller dosage in pigs (R)
• Black Cumin Seed Oil (R, R2, R3, R4).  Also brings it down when high (R, R2, R3)
• Mustard (R)

Top Supplements/Drugs

• Tea/EGCG
• Melatonin  (R),
• Niagen Nicotinamide NAD+/NAD+ (R),
• Curcumin (R),
• Probiotics: B fragilis (R), L Plantarum (R), S boulardii (R), L Casei (R), Bacillus Subtilis (R)
• Andrographis  (R)
• Baicalin (R) (not IL-4 or IL-5…only IL-10)
• Boswellia (R) – (in the body of study)
• Olive leaf/Oleuropein (R)
• Arabinogalactan (R)
• Vitamin D3 (R),