Cytokines, Certain Types & How to Encourage Healthy Function - Dr. Axe

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Cytokines: Their Key Role for Your Immune System & Inflammation Levels


Cytokines - Dr. Axe

Have you ever heard of cytokines? The term “cytokine” is actually derived from a combination of two Greek words: “cyto” meaning cell and “kinos” meaning movement. Cytokines play a major role in both health and disease, especially when it comes to inflammatory conditions, immune-related concerns like infections, trauma to the body, reproduction and even cancer.

According to one scientific article, which highlights their role in women’s health including preterm labor and endometriosis, “Progress in understanding of cytokine biology has led to appreciation of the importance of cytokines in every field of medicine.”

So what are cytokines? They are a category of small proteins that enable communication between cells. There are several families of cytokines which are produced differently, behave differently and have different activities in the body.

On the plus side, cytokines can help us to fight off infections and have a positive effect on our immune system and inflammation. However, when some cytokines don’t behave ideally or are overproduced, this can result in disease.

It can be difficult to explain cytokines without getting overly scientific, but by better understanding these powerful molecules, we may just be able to improve or even prevent some very common yet serious health concerns including arthritis, cancer and more.

What Are Cytokines?

A simple cytokines definition: A group of proteins made by the immune system that act as chemical messengers. Cytokines are proteins, peptides or glycoproteins secreted by lymphocytes and monocytes that regulate immune responses, haematopoiesis and lymphocyte development.

These small proteins act as messengers between cells, which is a really big deal since this includes carrying vital information that impacts and decides so many things in the body from embryonic development to modulating bone structure to maintaining homeostasis. Cytokines are probably best known for their key role as mediators and regulators of inflammatory responses. They are actually able to stimulate the movement of cells towards sites of infection, trauma and inflammation.

Cytokines are secreted by other cell types at high concentrations and can either affect the cell of origin (autocrine action), the cells closest to them (paracrine action) or distant cells (endocrine or systemic action). In general, they can act synergistically (working together) or antagonistically (acting in opposition). There are several different groups or families, which are structurally similar but have a diverse range of functions.

Keep in mind that although cytokines are absolutely essential to immune function, excessive amounts can actually become dangerous. A cytokine storm, also known as hypercytokinemia or cytokine release syndrome, is a condition caused by a surge in the production of inflammatory proteins.

This phenomenon was initially observed by physicians treating a case of graft-versus-host-disease in 1993, but has since been observed in many other conditions, including pancreatitis, bird flu and variola. Influenza is also thought to be one of the few conditions able to cause a cytokine storm and may account for the catastrophic effects of the 1918 influenza pandemic.

While researchers are still unclear exactly what causes a cytokine storm, it’s believed to be triggered when the immune system encounters a new pathogenic invader, causing the production of cytokines to skyrocket. This can result in significant damage to cells, tissues and organs and can cause serious side effects, including fever, fatigue, swelling, nausea and, in severe cases, organ failure and death.

Different Types

We now know that there are several subcategories that include both pro-inflammatory and anti-inflammatory cytokines. Pro-inflammatory cytokines are mainly produced by activated macrophages and are involved in the up-regulation of inflammatory reactions.

Scientific evidence has linked these pro-inflammatory proteins to a variety of diseases as well as the process of pathological pain. Meanwhile, anti-inflammatory cytokines are the molecules that help to regulate the immune system and control the pro-inflammatory cytokine response.

Here are the main families and their key characteristics or actions:

  • Chemokines: Direct cell migration, adhesion and activation
  • Interferons: Antiviral proteins
  • Interleukins: Variety of actions dependent upon the interleukin cell type
  • Monokines: Powerful molecules made by monocytes and macrophages that help to direct and regulate immune responses
  • Lymphokines: Protein mediators typically produced by lymphocytes (white blood cells) to direct the immune system response by signaling between its cells
  • Tumor necrosis factor: Regulate inflammatory and immune responses

There’s also erythropoietin, also called haematopoietin, which is a cytokine hormone that regulates red blood cell (erythrocyte) production.

Related: Ozone Therapy: Should It Be Approved for Medicinal Use?

4 Benefits of Cytokines

1. Immune System Regulation

The two principal producers of cytokines are T-helper cells and macrophages. What are those? T helper cells assist other cells in the immune response by recognizing foreign antigens and secreting cytokines, which then activate T and B cells. Macrophages surround and kill microorganisms, ingest foreign material, remove dead cells and boost immune responses.

By influencing and interacting with immune system cells, cytokines are able to regulate the body’s response to disease and infection. Cytokines affect both our innate and adaptive immune responses. Having an optimal production and behavior of our cytokines is key to the health of our immune systems.

One scientific article published in 2014 looked at the effects of cytokines like interferons (INFs) and interleukins (ILs) on mycobacterial infections, specifically tuberculosis. The researchers conclude, “Overall the IFN family of cytokines appears to be critical to the outcome of mycobacterial infection” and play a major role in containment of bacterial growth.

2. Helps Reduce Arthritis Pain

Since these proteins regulate various inflammatory responses, it’s no wonder that research is showing what a major role these proteins play in arthritis, an inflammatory joint disease. As mentioned earlier, overproduction or inappropriate production of certain cytokines by the body can result in disease.

According to a scientific article published in 2014 entitled “The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis,” interleukin 1-beta and tumor necrosis factor-alpha are believed to be the main inflammatory cytokines involved in osteoarthritis (OA) while interleukin-15 is linked to the pathogenesis of rheumatoid arthritis (RA).

While it’s clear that pro-inflammatory cytokines are at increased levels in arthritis patients, their anti-inflammatory versions have also been found in the synovium and in the synovial fluids of patients with RA. To date, research studies using animal models have demonstrated the ability of anti-inflammatory cytokines to reduce pain resulting from arthritis. However, they did not inhibit joint damage. Clinical trials with human subjects are ongoing and hopefully will result in some helpful findings for arthritis suffers soon.

3. Decrease Inflammation and Pain

I’m sure it won’t come as a surprise that anti-inflammatory cytokines are known for their ability to lower inflammation in the body, which is huge since we know that inflammation is at the root of most diseases. According to a scientific article titled, “Cytokines, Inflammation and Pain,” which was published in the journal International Anesthesiology Clinics, of all the anti-inflammatory cytokines, interleukin 10 (IL-10) has some of the strongest anti-inflammatory properties and is able to repress the expression of inflammatory cytokines such as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α).

IL-10 is also able to down-regulate pro-inflammatory cytokine receptors, so it’s able to decrease the production as well as the function of the pro-inflammatory cytokine molecules at multiple levels. According to this article, “Acute administration of IL-10 protein has been well-documented to suppress the development of spinally-mediated pain facilitation in diverse animal models such as peripheral neuritis, spinal cord excitotoxic injury, and peripheral nerve injury.”

In addition, recent clinical studies demonstrate that low blood levels of IL-10 and interleukin 4 (also an anti-inflammatory cytokine) may be big factors when it comes to chronic pain because it’s been found that patients struggling with chronic widespread pain have low concentrations of these two cytokines.

4. Helps Fight Cancer

Certain cytokines are now used in cancer immunotherapy, including the treatment of leukemia, lymphoma, melanoma, bladder cancer and kidney cancer. Our bodies naturally produce cytokines, but when used for natural cancer treatment, these proteins are created in a laboratory and then injected in larger doses than the body would typically make on its own.

According to the National Cancer Institute, interleukin-2 was the first cytokine found to have a therapeutic benefit on cancer. In 1976, Robert Gallo, M.D. and Francis Ruscetti, Ph.D. demonstrated hat this cytokine could “dramatically stimulate the growth of T and natural killer (NK) cells, which are integral to the human immune response.”

Almost 10 years later, another team of researchers led by Steven Rosenberg, MD, PhD, are said to have successfully cured several patients with advanced metastatic renal cell cancer (a type of kidney cancer) and melanoma by giving them interleukin-2. Interleukin-2 became the first cancer immunotherapy approved by the FDA in the U.S. To this day, it is still employed in the treatment of metastatic melanoma and renal cancer.

Side effects of interleukin-2 can include chills, fever, fatigue, weight gain, nausea, vomiting, diarrhea and low blood pressure. Rare but serious side effects include abnormal heartbeat, chest pain and other heart problems. Other interleukins are continuing to be being studied as possible cancer treatments.

How to Ensure a Healthy Balance of Cytokines

Cytokines are an important topic of scientific study that continues, but so far, it appears that a healthy diet rich in beneficial nutrients, exercise and stress reduction can all help to encourage a healthy balance of cytokines in the body.

It’s theorized that cytokines are generally affected by nutritional status. Chronic nutritional deficiencies have a negative impact on our immune response, which includes reductions in the production and activity of cytokines. So following a healing foods diet with lots of anti-inflammatory foods is a key way to boost the cytokine status of our bodies.

In vitro research has also shown that cinnamon extract increases interleukin-10 levels while down regulating pro-inflammatory cytokines in experimental models of induced inflammatory bowel disease.

There are also foods you’ll want to avoid, especially refined sugar. As the Arthritis Foundation points out, research has shown that processed sugars trigger the release of inflammatory cytokines.

A study published in the Journal of Physiology looked at the effects of prolonged strenuous exercise on pro-inflammatory and anti-inflammatory cytokines. The researchers found that while exercise increased some pro-inflammatory cytokines, plasma levels of anti-inflammatory interleukin-10 showed a 27-fold increase immediately post exercise and cytokine inhibitors were also released. So overall, the study suggests that exercise can increase anti-inflammatory cytokines, which help to decrease the inflammatory response that can result from prolonged strenuous activity.

Research has shown that at first, stress can cause the downregulation of inflammatory cytokines and the upregulation of anti-inflammatory cytokines. However, lasting chronic stress further increases proinflammatory cytokines, which then leads to inflammatory responses and can ultimately cause various diseases. So this is yet another reason to practice natural stress relievers on a daily basis.

Those suffering from cytokine storms should seek immediate medical attention. Treatment for this condition generally involves administering medications that neutralize specific cytokines, including TNF. Other approaches are also being investigated, including drug therapies that modulate immune function to prevent cytokine production from spiraling out of control.

Final Thoughts

  • What are cytokines? A group of proteins made by the immune system that act as chemical messengers.
  • There are several families of these signaling proteins including inflammatory or anti-inflammatory.
  • They are especially important to immune function and inflammatory responses.
  • Research continues, but so far, current or potential benefits include:
    • Immune system booster
    • Arthritis pain reliever
    • Pain reducer
    • Inflammation calmer
    • Cancer fighter
  • Ways to encourage healthy function and balance include a healthy whole foods–based diet that’s loaded with anti-inflammatory foods and leaves out inflammatory items like sugar. Stress reduction including regular exercise can also help to encourage optimal cytokine status.

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