Interleukins, Messenger Molecules, and Lupus

Interleukins are important messenger molecules in the immune system and many of them are associated with SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which means that the body’s immune system attacks its own cells and causes damage. Interleukins are an important part of the immune system and many of them are associated with SLE – but what, exactly, are interleukins?

What are Interleukins?

Interleukins are named for “Inter-” which means “to go between or among” and “Leukins” which are a family of heat-stable leukocytes, the name for the colorless blood cells that are involved in the immune system. In short, interleukins are “go-betweens,” allowing different parts of the immune system to communicate with each other and coordinate the body’s response to threats. You can read more about the immune system here. 

Interleukins primarily are involved with turning on and tuning inflammation up and down, where the body sends immune particles to the affected area to stop infections and clean up the debris. The body has several specific responses to diseases that it employs based on what it is facing, including lymphocytes that attack and ‘eat’ pathogens or a fever that heats up and potentially kills pathogens. You can read more about pathogens here.

How many Interleukins are there?

There are many kinds of interleukins – over 50 have been found encoded for in the human genome and there may be more we haven’t’ identified – and they are produced throughout the body, but all of them are involved in tuning the immune response to the pathogen. They are responsible for allowing leucocytes pass through the walls of blood vessels to combat infections, triggering parts of the brain that affect body temperature to cause fevers. They also affect the bloodstream by supporting the health and growth of blood and plasma cells and encouraging the production of antibodies and platelets. Some interleukins turn up the immune response by encouraging the release of cytokines and inflammation, while others block the production of cytokines and lymphocytes, turning the immune response down. Essentially, interleukins are how the body manages the immune system, acting as a thermostat of sorts. 

Interleukins are useful for cancer therapies because they can be made in a lab and can help the body’s immune system better fight off the cancer. However, in autoimmune diseases, the interleukins that turn down inflammation (including Interleukin-13 or IL13) are often not working properly, and the inflammation does not turn down at all. An example of correlation between interleukins and specific symptoms is IL-17, which is associated with nervous system and kidney symptoms of lupus. 

Interleukin levels can be measured with lab tests and are easily linked to more severe symptoms of autoimmune disease. This makes monitoring interleukins very useful in tracking disease activity over time and, in undiagnosed cases, detecting serious issues that could lead to a diagnosis.

Interleukins and Lupus

An antinuclear antibody test (ANA) is a laboratory test that uses a sample of blood to test if the immune system is producing antibodies to the nucleus proteins of healthy cells, a common factor in autoimmune diseases such as lupus. You can read more about them here. It can also measure interleukin levels.

When an interleukin encourages inflammation, this is usually right at the site of the problem. The area becomes warmer, and swells as immune cells flood the area. This is called “acute inflammation” and lasts only until the pathogen is defeated. Chronic inflammation is somewhat different and even has different cells, usually involving more cells that ‘eat’ the pathogen like macrophages and leukocytes. Chronic inflammation occurs throughout the body as a background noise that encourages damage to vulnerable areas such as the joints and organ tissues. Some interleukins such as Interleukin 6  or IL-6 actually seem to play two roles in inflammation – they are anti-inflammatory and turn down the more localized and temporary immune response, but start to cause problems during chronic inflammation. In the case of IL-6, it calls the alarm in an injured area and regulates lymphocytes as they are called to the site. It then also encourages more IL-6 to be produced. In chronic disease this feedback loop of IL-6 production continues to call lymphocytes to the area when not needed and does not trigger the destruction of lymphocytes already there. These lymphocytes and macrophages turn on the body’s own cells and destroy them.

In a 2020 study, IL-6 levels were found to be high in people with SLE and directly related to the severity of the disease. In the study, IL-1β, IL-6, IL-33, and TNF-α were measured in the blood of 200 people with SLE and 200 healthy controls. The study seemed to indicate that it’s not involved with inflammation specifically, and the researchers were not sure how it was involved. This is not uncommon – while we know generally how the immune system works, there is a lot happening “behind the curtain” in the body. We have only recently come to understand that interleukins can be produced by many different cells throughout the body and are still discovering new roles for many interleukins.

For example, Interleukin 33 (IL-33) is heavily involved in the pathogenesis of SLE. Previously, it was only thought to initiate type 2 immune responses, which involve immune cells produced in the thymus (t-cells) and is usually used to combat pathogens that come in via the skin or mucous-related areas such as the mouth and nose. As a result, the type 2 immune response involved in many allergic reactions. It has since been revealed to be involved in many other aspects of the immune response and plays a role in SLE. 

T-Cells, notably, are leukocytes made in the thymus that seek out and destroy threats to the body that use the body’s own cells to multiply. These threats include pathogens such as viruses and some bacteria, and also mutated cells that have become cancerous. They are essential to the body’s defense mechanism and there are therapies on the horizon that use lab-created T-cells to retrain the T-cells to avoid healthy cells, attack the immune system cells that mark healthy cells for destruction, or more aggressively attack tumors. One of the cell types that mark targets for destruction by T cells are various interleukins, and some also activate T cells and cause them to attack in the first place.

The immune system is also responsible for maintaining the microbiome of the mouth , skin, and gut. When the immune system is not working properly, it starts to react to and attack the beneficial microorganisms that share our body with us. As these tiny ecosystems are attacked, they lead to sickness and other problems, including infections, which makes the inflammation worse. The microbiome is now well-known to be a major player in lupus symptoms. 

SLE-related inflammation, caused by faulty interleukins, leads to fevers in 35-86% of patients, and fever is considered to be part of the “classic triad” of lupus, along with joint pain and the facial rash known as a “malar rash.” 

What can be done about Interleukins and Lupus?

In typically healthy individuals, inflammation goes away once the pathogens do. However, with lupus, the interleukins that cause inflammation continue to react to the body’s own cells. So, what can people with lupus do? 

In short, the immune system needs interleukins to function, but it needs those interleukins to be in-balance. It is the out-of-balance state that causes autoimmune diseases such as lupus. So medications that affect the overactive immune system are key to treating lupus and ends up effecting the interleukins as well.

Medications that suppress the immune system treat lupus by weakening the immune system and thus the autoimmune damage that it causes in the body. These immunosuppressant drugs typically aren’t affecting the interleukins directly but prevents certain chemical reactions from happening further back in the inflammation chain. For medicines that specifically affect interleukins, however, IL-6 is targeted by the drug Tocilizumab, which blocks IL-6 and reduces inflammation. Lupus medications such as NSAIDs and hydroxychloroquine reduce inflammation. NSAIDs block the production of certain cytokines, while HCQ makes lysosomes less functional in general, which can help the body get a handle on the immune system and regulate itself better.

Interleukin levels are tied to genetics, but can also be affected by stress, diet, exercise, and generally good health habits. It’s always a good idea to get regular exercise and eat a balanced diet, and the results can make a huge difference.

There is still so much about the immune system and interleukins that we do not know. This is why each person with lupus has to find, with the help of their treatment teams, the right combination of medication, diet, and lifestyle changes to reduce their symptoms and avoid flares. There are so many moving parts that each person is effectively unique.

You can read more about the cells that produce interleukins and other immune cells here.