TNF: Tumor Necrosis Factor

Updated May 13, 2019

This article was scientifically reviewed by YourDNA

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In the sometimes confusing world of DNA and genetics, TNF is one area it helps to know a lot about. Too much TNF can be a good thing if you're sick but if not, it can cause problems like rheumatoid arthritis and Chron's disease.

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Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

We know you want information you can trust in terms you can understand. This helps you make informed decisions, along with your medical team, about your health. Let's learn more about TNF.

What Is Tumor Necrosis Factor (TNF)?

Tumor necrosis factor (TNF), also known as cachexin or cachectin, is a type of messenger protein that’s generated by white blood cells in response to an infection or antigen that induces an immune response.

But it isn’t just any protein that helps fight viruses. TNF is a multifunctional cytokine, which is a cell signaling protein. It plays a role in:

  • Cell survival
  • Cell proliferation
  • Cell differentiation
  • Cell death

TNF, along with lymphotoxin (LT) alpha, is believed to be responsible for a number of other biological activities. Primarily they are known for beneficial inflammation and immune system activity by regulating immune cells.

But tumor necrosis factor malfunction can be harmful in some individuals and can cause autoimmune diseases if TNF production is excessive.

The first two types of TNF to be discovered were:

  • Tumor necrosis factor alpha (TNFa) is primarily produced when macrophages (immune system cells) are activated. There are two receptors that bind to TNF alpha: TNF-R1 and TNF-R2.
  • Tumor necrosis factor beta (TNF-β) is mostly generated by lymphocytes.

Since the discovery of TNF alpha and beta, 17 other TNF cytokines have been identified.

What Is the Structure of TNF

Tumor necrosis factor has a trimeric structure and crystal structure.

The trimeric structure has a crystallographic R-value of 19.7% and there are 3,477 protein atoms, 240 water molecules, one Tris molecule and one 2-propanol molecule.

Researchers have primarily studied mouse TNF structure, which is very close in makeup to human TNF structure save a few key differences. TNF is unique in that it can now be reproduced in a laboratory.

Tumor Necrosis Factor Superfamily

As noted above, there’s more than one type of TNF. Tumor necrosis factor superfamily refers to a large grouping of type II transmembrane proteins with TNF homology that function as a cytokine.

They are mostly expressed from immune cells known as macrophages.

The TNF superfamily includes:

  • TNF alpha
  • Lymphotoxin alpha (TNF beta)
  • Lymphotoxin beta
  • OX40 ligand
  • CD40 ligand
  • Fas ligand
  • CD27 ligand
  • CD30 ligand
  • TNF-related apoptosis-inducing ligand
  • CD254
  • TNF-related weak inducer of apoptosis.
  • A proliferation-inducing ligand
  • B-cell activating factor
  • Vascular endothelial growth inhibitor
  • TNF superfamily member 18
  • Ectodysplasin

There are 19 members of the TNF superfamily in total. The core members are lymphotoxin (LTalpha), LTbeta, TNF and LIGHT. There’s also a TNF receptor superfamily with 29 members the include TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.

What Is the Function of the TNF Gene

We now know genes are responsible for regulating even the smallest of components and activities in the body.

The TNF gene is responsible for encoding the cytokine that drives the TNF superfamily.

Therefore, the TNF gene is connected to everything the cytokine does, which is a wide variety of biological activities. Cytokine functions through the receptors it binds to.

Once it binds, cytokine helps regulate lipid metabolism, cell proliferation, apoptosis, cell differentiation and coagulation.

Health Conditions Related to TNF

TNF can be both a positive and negative to a person’s health. Because tumor necrosis factor is an integral part of the immune system, it can be argued that it’s related to every illness.

The production of TNF can help boost the immune system to fight off diseases. At the same time, there are a number of health conditions that have been associated with tumor necrosis factor because of the inflammation it produces.

TNF immunology has been focused on arthritis and IBD conditions, but TNF-related conditions vary significantly.

Tumor Necrosis Factor and Cancer

Cancer researchers are particularly interested in learning more about TNF. Not only does it appear to boost immune response, but there’s also evidence that TNF kills some types of tumor cells.

TNF and Obesity

People who are overweight produce an excess amount of TNF. The end result could be an increased risk of insulin resistance.

TNF and Psoriasis

People who have psoriasis experience red, inflamed skin plaques. This symptom of the disease is caused by high levels of TNF.

Tumor Necrosis Factor and Type II Diabetes

Research has found links between TNF and insulin resistance that leads to type II diabetes.

TNF and Autoimmune Disease

The TNF cytokine is associated with an array of autoimmune diseases. It doesn’t cause the autoimmune disease per se, however, high levels of TNF can make symptoms worse due to increased inflammation.

Tumor Necrosis Factor and Cachexia

Cachexia is the medical term for fatigue and wasting that’s connected to chronic illness. Medical researchers now believe TNF cytokine plays a key role in cachexia.

TNF and Inflammatory Bowel Disease (IBD)

IBD is marked by inflammation in the intestinal tract. Medical researchers have reported that the number of people with an IBD is increasing. Treating IBD involves identifying the type of TNF that’s causing the inflammation. Once the TNF is identified an appropriate anti-TNF drug can provide significant relief.

TNF and Crohn’s Disease

Crohn’s disease is an inflammatory condition in which there is chronic inflammation in parts of the gastrointestinal tract. The condition affects more than 20 people per 100,000.

Crohn’s disease treatment includes the use of TNF inhibitors. The practice was approved in 1998 and has helped many Crohn’s disease patients go into remission.

Tumor Necrosis Factor and Ulcerative Colitis

Ulcerative colitis is a type of inflammatory bowel disease that affects more than 200,000 people in the U.S. The condition can be quite uncomfortable, typically lasting a few years or even a lifetime.

Tumor necrosis factor is believed to play a significant role in the development of ulcerative colitis because it is present in the stool of individuals with ulcerative colitis.

TNF and Arthritis

TNF is perhaps best known for its connection to various forms of arthritis. In addition to causing inflammation, tumor necrosis factor inhibits regulatory T-cells in people who have rheumatoid arthritis.

How Does TNF Cause Inflammation?

TNF is a pro-inflammatory cytokine that’s secreted from inflammatory cells. The protein both causes inflammation and helps to regulate it.

TNF sends signals to other cells that cause inflammation, which results in inflammation in a certain area of the body. When there is excess TNF in the blood it can cause inflammatory conditions such as arthritis and irritable bowel syndrome.

A fair amount of research has gone into measuring TNF among those with rheumatoid arthritis. In multiple studies, researchers measured and compared TNF serum levels of RA patients to a control group without the disease.

TNF levels in rheumatoid arthritis sufferers are consistently elevated. It’s the TNF that causes joint inflammation, swelling and redness.

Signs of High TNF

TNF production is tightly regulated in the majority of people. If you’re among the unlucky minority that has excessive TNF, you’ll probably experience symptoms.

Having inflammation-related diseases is an indicator that TNF levels may be elevated. Other signs of high TNF include:

  • Fever
  • Loss of appetite
  • Low blood sugar
  • Redness to a wounded area
  • Swelling
  • Muscle aches

Because TNF is produced in response to a perceived infection, the signs closely mirror general symptoms of illness. High TNF levels suggest inflammation that’s helping the body heal.

However, if no infection is present that could mean the immune system isn’t working properly.

Testing for TNF

TNF is detected by measuring serum levels in the blood plasma. Basic TNF blood tests determine TNF-alpha (TNF-a) levels and evaluate a person’s cytokine profile.

It’s a very simple, straightforward test that doesn’t require fasting.

Other tests may be recommended and can be done at the same time. They include:

  • Interferon-alpha test
  • Interleukin-1 test
  • Interleukin-2 test
  • Interleukin-6 test

One type of TNF test is used in rheumatoid arthritis patients to predict TNF inhibitor response by measuring the ratio of interferon (IFN)-alpha to IFN-beta. The results help determine which anti-TNF drug will be the best treatment option.

What Are Tumor Necrosis Factor Inhibitors?

A tumor necrosis factor inhibitor, also known as a TNF blocker or biological therapy, is a substance that blocks or limits the production of TNF.

Two common TNF inhibitors are monoclonal antibodies and circulating receptor fusion protein.

There are inhibitor drugs created specifically to block excess TNF in patients with rheumatoid arthritis and autoimmune diseases to prevent excessive inflammation. The drugs are created using animal or human tissue in a laboratory.

The TNF inhibitor enters the bloodstream where it then triggers the immune system to block inflammation.

The TNF inhibitor drug class includes the following FDA-approved therapies:

  • Infliximab (Remicade)
  • Infliximab-abda (Renflexis)
  • Infliximab-dyyb (Inflectra)
  • Etanercept (Enbrel)
  • Etanercept-szzs (Ereizi)
  • Adalimumab (Humira)
  • Adalimumab-adbm (Cyltezo)
  • Adalimumab-adaz (Hyrimoz)
  • Adalimumab-atto (Amjevita)
  • Certolizumab pegol (Cimzia)
  • Golimumab (Simponi, Simponi Aria)

Typically, TNF inhibitor therapies take 2-4 weeks to take full effect. Patients may experience continued improvements for up to six months.

Tumor necrosis factor inhibitors are administered via IV infusion or injections. Inhibitors that are given as a shot should be done in the doctor’s office before patients attempt to give themselves shots at home.

The shots must to given once every 1-4 weeks. Infusion inhibitors are given in the doctor’s office once every 4-8 weeks.

Regardless of the tumor necrosis factor inhibitor that’s taken it will be a long-term therapy. The time between doses may be extended, however, inflammation will return if a patient stops taking the drugs altogether.

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