What is inflammation?

Inflammation is the body’s protective response to tissue injury, infection (e.g. bacteria, viruses) and other harmful stimuli/agents.

It involves the release of inflammatory molecules, known as cytokines, that recruit and coordinate immune cells (e.g. white blood cells) in an effort to remove the harmful agent, prevent further tissue damage and promote healing.

Inflammation as a short-term, proportional response to injury (i.e. acute inflammation) is often beneficial and helps recovery. When inflammation is excessive or persists for a long time (i.e. chronic inflammation), however, it can cause damage to the body.

We've covered inflammation in greater detail in the Inflammation and IL-6 trait article. Readers are encouraged to visit that article for a more in-depth background on inflammation.

KEY POINTS

• Inflammation is the body's immune response to harmful stimuli such as bacteria, toxic substances or injured cells.
• Acute inflammation is short-term and is often beneficial in clearing the harmful stimuli and promoting healing.  
• Chronic inflammation lasts a long time and often causes unwanted damage to other tissues in the body.
• Inflammation involves the release of molecules called cytokines that coordinate the inflammatory response.
  

What are cytokines?

In order to coordinate an effective inflammatory response, several different cells need to communicate with each other.

For example, mast cells, which release histamine to dilate blood vessels and allow immune cells to enter a site of tissue injury, may need to communicate with B-cells, which can secrete antibodies to neutralise a pathogen. B cells, in turn, may need to signal to macrophages so that they engulf the neutralised pathogen.

So, how do these cells communicate with each other? This is where cytokines come in. Cytokines are signalling proteins secreted by cells of the immune system that help to coordinate and regulate an inflammatory response.

Source: Zhang, J. M., & An, J. (2007). Cytokines, inflammation and pain. International anesthesiology clinics, 45(2), 27.

There are lots of different cytokines, which form a complex communication network and have different effects on the inflammatory response.

Broadly speaking, some cytokines help to initiate, stimulate, and sustain inflammation by activating immune cells. These are known as pro-inflammatory cytokines, and include: IL-1, IL-18, TNF-α. Pro-inflammatory cytokines are extremely important for targeting, neutralising and clearing pathogens e.g. bacteria, viruses etc.

Other cytokines act to suppress or terminate inflammation and play an important role in resolution of tissue injury and tissue healing. These are known as anti-inflammatory cytokines, and include: IL-4, IL-10, and TGF-β.

Some cytokines, such as IL-6, are variable, and can act as both pro- and anti-inflammatory cytokines under different circumstances.

KEY POINTS

• Cytokines are signalling proteins that help to coordinate an inflammatory response.
• Pro-inflammatory cytokines stimulate inflammation.
• Anti-inflammatory cytokines suppress inflammation.

How does cytokine balance affect susceptibility to inflammation?

The balance of pro- and anti-inflammatory cytokines in a tissue’s local environment strongly influences whether or not that tissue is undergoing an inflammatory response.

For example, in the early stages of bacterial infection, immune cells secrete lots of pro-inflammatory cytokines to ensure that the bacteria are neutralised, engulfed by macrophages, and removed.

By contrast, in the later stages after infection, more anti-inflammatory cytokines are produced to help terminate the inflammatory response and allow tissues to heal.

For example, in the diagram below, we can see that pro-inflammatory cytokines (illustrated by red dots) predominate in the early stages following tissue injury (e.g. infection, physical trauma, other cell damage).

After the peak of inflammation, more anti-inflammatory cytokines (illustrated by blue dots) are released, which dampen down inflammation and promote tissue repair.

Source: Placek, K., Schultze, J. L., & Aschenbrenner, A. C. (2019). Epigenetic reprogramming of immune cells in injury, repair, and resolution. The Journal of clinical investigation, 129(8), 2994-3005.

When we look at the long-term environment of tissues, there needs to be a fine balance between pro- and anti-inflammatory cytokines.

If there is a relative excess of pro-inflammatory cytokines, this can increase our risk of excessive, uncontrolled, or prolonged inflammation (i.e. chronic inflammation) that causes damage to our own tissues. Tissue damage from chronic inflammation, in turn, is thought to several different diseases e.g. Type II diabetes, heart disease, and age-related macular degeneration, as well as ageing.

Source: Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018). Age and age-related diseases: role of inflammation triggers and cytokines. Frontiers in immunology, 9, 586.

By contrast, if the balance is excessively tipped towards anti-inflammatory cytokines, this can increase our susceptibility to infection, as we cannot effectively mount an inflammatory response when faced with pathogens (e.g. bacteria, viruses).

Source: Bello, R. O., Chin, V. K., Abd Rachman Isnadi, M. F., Abd Majid, R., Atmadini Abdullah, M., Lee, T. Y., ... & Basir, R. (2018). The role, involvement and function (s) of interleukin-35 and interleukin-37 in disease pathogenesis. International journal of molecular sciences, 19(4), 1149.

A cytokine balance that is tipped towards inflammation is sometimes known as a ‘pro-inflammatory cytokine profile.’ If we were to analyse the levels of different cytokines of a local tissue environment with a pro-inflammatory profile, we would find higher levels of pro-inflammatory cytokines (e.g. TNF-α) and/or lower levels of anti-inflammatory cytokines (e.g. IL-10).  

As mentioned previously, a pro-inflammatory cytokine profile can increase our susceptibility to chronic inflammation and its associated health conditions.

KEY POINTS

• The balance of pro- and anti-inflammatory cytokines affects our susceptibility towards inflammation.
• A balance tipped towards pro-inflammatory cytokines can increase the risk of chronic inflammation and associated health conditions (e.g. heart disease, Type II diabetes, rheumatoid arthritis).
• Excessive production of pro-inflammatory cytokines and/or low production of anti-inflammatory cytokines can lead to a pro-inflammatory cytokine balance.

What is IL-10?

IL-10 stands for Interleukin-10. It is one of the body’s anti-inflammatory cytokines that acts to suppress inflammation.

IL-10 is produced by several different cells, including immune cells as well as non-immune cells, including epithelial cells that line the surfaces of various organs. When secreted, IL-10 binds to specialized receptors on cells and then switches on genes that code for various anti-inflammatory proteins. Similarly, Il-10 switches on anti-inflammatory genes and enhances production of various pro-inflammatory cytokines.

The IL-10 cytokine is coded for by your IL10 gene. Variants of this gene can affect how much IL-10 you produce, which, in turn, can influence your cytokine balance and susceptibility to inflammation.

KEY POINTS

• IL-10 (Interleukin-10) is an important anti-inflammatory cytokine.
• IL-10 helps to suppress inflammation by switching off pro-inflammatory genes and switching on anti-inflammatory genes.
• Your IL10 gene codes for the IL-10 cytokine.
• Variants of the IL10 gene can affect production of IL-10 and therefore your cytokine balance.

How do IL10 gene variants affect cytokine balance?

A SNP (Single Nucleotide Polymorphism), designated rs180096, causes a A-->G change in the DNA code of the IL10 gene, creating two different IL-10 gene variants or ‘alleles’: the ‘A’ allele and the ‘G’ allele.

Some studies suggest that the ‘A’ allele is linked to lower expression of the IL10 gene and therefore lower production of the IL-10 cytokine.

In turn, lower production of the anti-inflammatory IL-10 cytokine may, other things being equal, tip the cytokine balance in favour of inflammation.

The ‘A’ allele of IL10 gene can therefore be thought of as genetic factor that predisposes someone towards a pro-inflammatory cytokine profile. People who inherit the ‘A’ allele may therefore be at greater risk of developing chronic inflammation and health conditions linked to chronic inflammation.  

KEY POINTS

• The ‘A’ allele (rs180096) of the IL10 gene is linked to lower production of the anti-inflammatory IL-10 cytokine.
• The ‘A’ allele may predispose someone towards a pro-inflammatory cytokine balance/ profile.
• People who inherit the ‘A’ allele may be at greater risk of chronic inflammation.

How do IL10 gene variants affect susceptibility to chronic inflammation and related health conditions?

As mentioned in the previous section, the ‘A’ allele (rs1800896) of the IL10 gene is linked to a pro-inflammatory cytokine profile, which increases the risk of inflammation.

On this note, several studies have found that, compared to the ‘G’ allele, the ‘A’ allele is more frequently observed in individuals with various inflammatory health conditions, such as: rheumatoid arthritis, acute pancreatitis, and inflammatory bowel disease (e.g. Crohn’s disease, ulcerative colitis).

Similarly, a pro-inflammatory cytokine profile may predispose a person towards developing chronic, low-grade inflammation. As explained in the Inflammation and IL-6 trait article, chronic inflammation can cause damage to our own tissues and cells, including neurons, muscle cells, liver cells, and blood vessels. This cell and tissue damage from chronic inflammation, in turn, is thought to underlie the development of various diseases, including cardiometabolic diseases such as Type II diabetes, heart disease, and atherosclerosis (the build-up of fatty plaques in blood vessels).

In this respect, a pro-inflammatory cytokine profile with lower levels of anti-inflammatory cytokines (e.g. IL-10) may enhance susceptibility to cardiometabolic disease.

Kleemann, R., Zadelaar, S., & Kooistra, T. (2008). Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovascular research, 79(3), 360-376.

On this note, studies have linked the ‘A’ allele of the IL10 gene to a higher risk (compared to those without the ‘A’ allele) of coronary artery disease, ischaemic stroke, and Type II diabetes.

Chronic inflammation is also thought to drive ageing. Interestingly, people who do not carry the ‘A’ allele of the IL10 gene (i.e. those with GG genotype) may produce higher levels of IL10 and have a more anti-inflammatory cytokine profile associated with greater longevity.

In one study, it was found that the GG genotype was more frequently represented in Italian centenarian (i.e. aged 100 years and over) men.  

KEY POINTS

• The ‘A’ allele of the IL10 has been linked to a higher risk of chronic inflammation, inflammatory diseases, and cardiometabolic diseases.
• The ‘GG’ genotype has been associated with a more anti-inflammatory cytokine profile.

Your IL-10 and anti-inflammation trait

Your IL-10 and anti-inflammation trait analyses variants of your IL10 gene based on the rs1800896 SNP and assesses your production of the anti-inflammatory cytokine, IL-10.

You will be classified into one of two groups:

• Reduced IL-10 production - you carry the 'A' allele linked to a more pro-inflammatory cytokine balance.
• Normal IL-10 production - you have the GG genotype linked to a more anti-inflammatory cytokine balance.

To find out your result, please login to truefeed.

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