Inflammation is a buzzword used frequently in conversations about health. Many treatments and interventions for various conditions have the goal of decreasing inflammation. But what does inflammation mean in the context of autoimmune disease, and how do we measure it?

Inflammation markers can give insights into your current health status and progression of autoimmune disease. If you have high levels of certain inflammatory markers, you may be able to intervene to slow the progression or lessen the symptoms of your autoimmune disease.

What Do We Know About Inflammation in Autoimmune Disease?

Inflammation is one of the body’s natural defenses against illness and disease, but it can also be harmful if it persists for too long. Scientists don't fully understand the causes of autoimmune disease, but they do know that inflammation and inflammatory markers are typically higher in people with these conditions. Several factors can trigger autoimmune diseases, including genetics, environmental exposures, and lifestyle choices.

What Is Inflammation?

Inflammation is your body’s immune response to injury and foreign substances. It is one of the first lines of defense against pathogens, such as bacteria, viruses, and toxins, and is an important part of wound healing after injuries such as cuts, burns, or surgery. Inflammation is a normal response by the body to protect itself from infections and tissue damage. (Source, Source)

The immune system mounts its defense by sending white blood cells and other molecules to attack foreign invaders. When there are no foreign invaders present, however, this response can cause damage to normal tissue. Inflammation is a complex process that involves many different cell types and chemicals that trigger a cascade of events.

What Is a Pro-Inflammatory Immune Response?

During an pro-inflammatory immune response, signals are sent through the bloodstream to recruit “first responders” that attack the problem and resolve it as soon as possible. This response involves blood vessels dilating, fluid moving from blood vessels into surrounding tissues, and white blood cells rushing to the site of injury. (Source)

The main biological players involved in the response are inflammatory cells and cytokines (signaling molecules).

Inflammatory cells are white blood cells, called macrophages, that travel through the blood to the site of injury. They arrive at a site and release cytokines, which recruit other immune cells. These recruited cells then produce their own additional cytokines and start differentiating into different types of cells, such as neutrophils or more macrophages. This coordinated attack cleans up debris and kills bacteria by releasing chemicals that destroy them.

Cytokines help coordinate this attack and activate other cells. There are many different types of cytokines involved in the inflammatory process, which we will explore later. Some of the major players include interleukins (IL), tumor necrosis factors (TNFs), and acute phase proteins, such as C-reactive protein (CRP). (Source, Source)

Acute Inflammation vs. Chronic Inflammation

Inflammation is a highly regulated process and can be categorized as acute (short-lived) or chronic (long-lasting), which can have vastly different implications for health. Acute inflammation is generally protective — it fights infections and starts your body’s healing process — whereas chronic inflammation can become damaging when there is no longer an instigating agent present in your body.

Acute inflammation is your body’s immediate response to sudden trauma or damage. It typically occurs within 1 to 4 hours of the injury or infection, peaks after about 2 days, and then begins resolving. On the other hand, chronic inflammation is your body’s prolonged response when there’s no injury or infection requiring a reaction. Chronic inflammation is generally defined as inflammation that lasts more than 3 months. (Source)

Signs of Inflammation

Acute inflammation is distinguished by commonly recognized signs, such as redness, swelling, slight pain, and heat within the region that has been injured or damaged. In contrast, the signs of chronic inflammation are harder to see with the naked eye and may not be recognized or identified. In the early stages of some autoimmune diseases, you might not experience major symptoms for years.

Signs of acute inflammation include:

• redness, swelling, and pain in the area that has been injured or damaged
• heat in the area that has been injured or damaged
• fever
• tiredness
• cold hands and feet
• muscle aches
• headaches

Signs of chronic inflammation include those listed above, as well as:

• excess weight
• insulin resistance
• trouble sleeping
• mood issues
• skin rash
• pain in the muscles, joints, or spine
• abdominal or chest pain
• constipation or diarrhea
• gas or bloating after meals
• acid reflux (heartburn)

(Source, Source, Source, Source)

What Causes Chronic Inflammation?

Chronic inflammation can lead to serious health problems, such as heart disease and high blood pressure, and may be making symptoms of autoimmune diseases more severe and less manageable. It’s important to understand the factors that may contribute to your risk of developing or increasing chronic inflammation, so that you can take steps toward reducing it.

Some lifestyle factors that can raise inflammation include:

• drinking alcohol in excess
• having a high body mass index (BMI), unless it’s a result of being very muscular
• exercising at maximum intensity too frequently, or not exercising enough
• experiencing chronic stress
• smoking tobacco

(Source, Source, Source)

What Are Inflammation Markers?

Broadly, markers of inflammation are proteins and other molecules produced in response to an inflammatory process. They are substances found in blood that reflect the activity of inflammation within the body. These markers can be measured through a simple blood test and can be used to help diagnose and monitor various health conditions. (Source)

Health care practitioners can use several different tests for measuring inflammatory markers, depending on what they suspect is causing inflammation in your body. While inflammatory markers can be helpful in determining if you have an infection or other condition that causes inflammation, they can also be indicative of autoimmune disease. Tests for inflammation are often used as part of an initial screening and diagnostic process for autoimmune diseases such as Hashimoto's thyroiditis, celiac disease, rheumatoid arthritis, lupus, Crohn's disease, and ulcerative colitis. (Source)

It is important to note that while these markers can be indicative of inflammation, tests for inflammatory markers are nonspecific, meaning they can show that inflammation is present but not what may be causing it.

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What Do High Levels of Inflammation Markers Mean?

These markers provide important information about the presence, severity, and progression of inflammation in the body. A high level of an inflammatory marker can indicate the presence of an infection or an autoimmune disease. The level of these markers can also be used to monitor the progression of a disease over time.

For example, if the level of an inflammatory marker is high at the time of diagnosis and then decreases with treatment, this can indicate that the treatment is working to control the inflammation. In contrast, if the level of an inflammatory marker remains high or increases over time, this can suggest that the treatment is not effective or that the disease is progressing. Additionally, these markers can also be used to monitor response to therapy, and to determine the prognosis of a disease. (Source)

Common Inflammation Markers

Outlined below are the inflammatory markers commonly used to assess inflammation in autoimmune diseases.

C-Reactive Protein (CRP)

The most common inflammatory marker is C-reactive protein (CRP). Produced by the liver, CRP is known as an acute phase reactant because its levels increase during acute inflammation. It is a nonspecific marker of inflammation, but is commonly elevated in autoimmune diseases such as rheumatoid arthritis, lupus, psoriatic arthritis, and scleroderma. In these conditions, CRP can be used to monitor disease activity and response to treatment. (Source, Source)

C-reactive protein plays a role in the innate immune response, which is the body's first line of defense against infection and injury. It binds to the surface of most bacteria as well as dead or dying host cells. When CRP attaches to a microorganism or cell, it triggers an immune response by recruiting various other immune cells to help attack and eliminate the problem.

C-reactive protein also promotes the formation of blood clots, which helps to stop bleeding and repair damaged tissues. High CRP levels can indicate damage to blood vessels and may be seen in conditions such as stroke or heart attack. (Source)

Following CRP levels is useful in monitoring response to therapy and determining prognosis. Elevated CRP levels can indicate a flare-up of symptoms and may suggest the need for a change in treatment. Conversely, a decrease in CRP levels can indicate that treatment is effectively controlling inflammation.

Erythrocyte Sedimentation Rate (ESR)

A complementary test for inflammation is erythrocyte sedimentation rate (ESR). The ESR test measures how fast red blood cells settle out in a tube of blood after being spun down. When there is inflammation in the body, the level of certain proteins in the blood increases. These proteins cause the red blood cells to clump together and fall to the bottom of the tube at a faster rate. The faster the red blood cells fall, the higher the ESR.

If your ESR is high it could indicate inflammation somewhere in your body, but it does not tell you where the inflammation is located or what caused it. An ESR is usually used as part of an initial evaluation for people who may have an inflammatory condition. It can also be used periodically during treatment if there is concern about relapse or flare-ups of an autoimmune disease. (Source)

Plasma Viscosity (PV)

Another test for inflammation is plasma viscosity (PV), which measures the thickness of blood. Plasma viscosity is determined by measuring the flow rate of blood plasma through a small tube at different speeds. The thicker the blood, the higher the plasma viscosity. (Source)

Changes in plasma viscosity can be caused by different factors, such as changes in red blood cell count or the presence of certain proteins in the blood. Inflammation causes the body to produce higher levels of acute phase proteins and fibrogen, which make blood thicker. Additionally, cytokines that are produced in response to inflammation stimulate production of more red blood cells, which also makes blood more viscous. Certain autoimmune conditions such as lupus, arthritis, and inflammatory bowel disease can cause red blood cells to become more “sticky,” resulting in increased plasma viscosity. Conversely, conditions such as anemia can cause the blood to thin, resulting in decreased plasma viscosity. (Source)

Plasma viscosity can be used to diagnose diseases, monitor their progression or response to treatment, and assess risk factors for various conditions at an early stage. It is a nonspecific test, but it can provide valuable information when used in conjunction with other tests such as ESR, CRP and white blood cell count. Plasma viscosity is used less frequently than ESR, but it is still widely used in the medical field, especially when ESR is inconclusive or not reliable. (Source)

Tumor Necrosis Factor Alpha (TNF-α)

Tumor necrosis factor alpha (TNF-α) plays a crucial role in the body's inflammatory response. It stimulates activation of pro-inflammatory cytokines and enzymes, as well as adhesion of cells and other debris to blood vessels. It also plays a role in the regulation of cell growth, division, and death. High levels of TNF-α can indicate an increased inflammatory state. (Source)

Tumor necrosis factor alpha is implicated in the pathogenesis of autoimmune diseases by promoting inflammation and tissue damage. In rheumatoid arthritis, for example, TNF-α contributes to destruction of joints. In psoriasis, it leads to overproduction of skin cells. In inflammatory bowel disease, TNF-α is produced in the gut and contributes to the inflammation of the intestinal lining. Targeting TNF-α with anti-TNF therapy has been shown to be an effective treatment for a number of autoimmune diseases. (Source, Source, Source)

Fibrinogen

The protein fibrinogen is a crucial component of the extracellular matrix, which gives structural support to cells and tissues. However, when fibrinogen is overproduced, as is the case in several autoimmune diseases, it can lead to the formation of scar tissue. Excessive formation of fibrinogen leads to overly fibrous connective tissue and progressive organ damage. (Source) ​​

In rheumatoid arthritis, fibrinogen is produced in the joints and contributes to joint damage and loss of function. In systemic sclerosis (scleroderma), fibrinogen is produced in the skin and internal organs, leading to thickening of the skin and damage to organs. In lupus, fibrinogen is produced in various tissues, including the skin, joints, and kidneys, leading to organ damage. (Source, Source)

Ferritin

Ferritin is a protein that stores iron in cells. It is found in almost all tissues of the body and serves as a reservoir for iron, which is used for the production of hemoglobin (the protein that carries oxygen in red blood cells). Ferritin levels in the blood can be measured as a marker of iron stores in the body and can be used to diagnose and monitor iron deficiency anemia and other iron-related disorders. (Source)

Ferritin is often used as an indicator of inflammation in the body because it is produced by immune cells as well as by other cells involved in the inflammatory response. In autoimmune diseases, ferritin levels can be elevated in the presence of inflammation due to pro-inflammatory cytokines such as IL-1 and TNF-α. These cytokines stimulate the production of ferritin in the liver and other tissues, leading to an increase in ferritin levels in the blood. (Source)

Interleukin-2 (IL-2)

Interleukin-2 (IL-2) is a type of cytokine that activates several types of inflammatory cells and cytokines. It is also involved in the differentiation of T cells, which have a key role in preventing autoimmunity. Interleukin-2 can be detected in the serum or plasma of healthy individuals at low levels but has been shown to increase during inflammation. (Source, Source)

In autoimmune disorders, IL-2 plays a complex role. On one hand, IL-2 is necessary for the activation and proliferation of T cells, which can lead to the development of autoimmune diseases. On the other hand, IL-2 also promotes the differentiation of regulatory T cells, which can help to suppress the immune response and prevent autoimmune disease. (Source, Source)

Interleukin-6 (IL-6)

Interleukin-6 (IL-6) is a pro-inflammatory cytokine that helps to stimulate the production of antibodies and white blood cells to fight infection. IL-6 is produced where inflammation is found in the body, and advances the area from acute inflammation to chronic inflammation by activating T cells and differentiating B cells. IL-6 also promotes the synthesis of CRP in the liver, as well as the production of TNF-α and other cytokines. (Source)

Elevated levels of IL-6 can be found in autoimmune diseases, chronic inflammation and infections, and normal pregnancy. In lupus, IL-6 is produced by activated B cells and contributes to the inflammation and tissue damage seen in the disease. It also plays a role in the production of autoantibodies, which are a hallmark of lupus. (Source)

Interleukin-10 (IL-10)

Interleukin-10 (IL-10) is a cytokine that helps regulate the immune response. It can inhibit the production of pro-inflammatory cytokines and suppress the activation of pro-inflammatory immune cells, including T cells and macrophages. Its action helps to prevent excessive inflammation and tissue damage. (Source, Source)

In autoimmune disorders, IL-10 has been shown to have anti-inflammatory effects and can help to suppress the immune response. Studies have shown that patients with autoimmune disorders, such as inflammatory bowel disease, often have lower levels of IL-10, and that increasing IL-10 levels can help to reduce inflammation and improve symptoms. (Source)

The Bottom Line on Inflammation Markers

Inflammation can be a result of injury, infection, or disease. While acute inflammation is protective, chronic inflammation can be a precursor to much larger issues. Chronic inflammation can contribute to progression of autoimmune diseases, exacerbate symptoms, and lead to other health problems.

Although there are many different inflammation markers, the ones listed are among the most common. Measuring and monitoring markers of inflammation, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and plasma viscosity (PV), can give crucial insights into your health status. You can start a conversation with your health care provider if you think you are at risk for high levels of inflammatory markers.

If you have an autoimmune condition, consuming anti-inflammatory foods and anti-inflammatory drinks can help manage your symptoms. A diet rich in antioxidants, flavonoids, and polyphenols may help to reduce inflammation. (Source)

WellTheory’s expert Care Team can support you in making diet and lifestyle changes that reduce inflammation and improve your autoimmune health.