What Is TNF (Tumor Necrosis Factor)?

Medically Reviewed by Zilpah Sheikh, MD on November 14, 2023
Written by Kendall K. Morgan
9 min read

Tumor necrosis factor (TNF) is a protein you have in your body. It's important for your immune system to work the way it should to protect you. It's also involved in healing. 

TNF works by causing inflammation. When you have too much TNF or it doesn't go away when you stop needing it, you'll have chronic inflammation. When this happens, it can cause you to have an autoimmune or inflammatory disease, such as rheumatoid arthritis.

TNF also makes tumors die from the inside out. Doctors may call this process necrosis. That's where tumor necrosis factor gets its name. Scientists discovered its role in tumors and cancer before they knew about the other things it does. 

When you have an infection, certain white blood cells release chemicals that tell other cells to cause inflammation. Your doctor might call them signaling chemicals or cytokines. They act as chemical messengers in your body. TNF is one type of cytokine. It's a major player when it comes to triggering inflammation. 

It may surprise you to learn that inflammation is sometimes a good thing. It happens when your immune system – your body's natural defense force – is fighting a possible threat. For example, when you have a cold, your sinuses swell. When you get a cut, your finger turns warm and red. These things don't feel good, but they show that your immune system is doing its job.

When you're healthy, other cytokines will tell your body to stop the inflammation once the threat is gone. Sometimes, this process doesn't work right and you'll keep having inflammation that isn't good for your body. If you have a disease like rheumatoid arthritis or psoriatic arthritis, your immune system is confused about what to attack. It goes after healthy body parts, like your joints, by mistake. Your system gets flooded with inflammation, which often means you have too much tumor necrosis factor – specifically, a type called TNF alpha.

You can think of the white blood cells that make TNF as the army. TNF is the signal that tells the rest of the defense units where to go and what to do. These defense units do different things. Some white blood cells fight infection. TNF also tells other cells to make other chemicals, like the hormones that cause you to lose your appetite when you're sick. It's all part of the inflammatory process.

If you have a severe bacterial infection like pneumonia, high levels of tumor necrosis factor are a sign of inflammation that's helping you heal. But high TNF levels can also trigger some symptoms that won't feel good, including:

  • Low blood pressure
  • Fever
  • Muscle aches
  • Loss of appetite
  • Redness and swelling (if you have an infected wound)

 

If you have a lot of TNF but no infection or injury, your immune system may not be working right. Symptoms are usually different from when you have an infection. For example, if you have psoriasis, high levels of TNF play a role in the raised, red skin plaques that come with the disease. For people with arthritis, they play a role in joint swelling and redness, also known as joint inflammation.

The inflammation from too much TNF alpha can lead you to have many diseases, including:

  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Juvenile arthritis
  • Ankylosing spondylitis
  • Inflammatory bowel disease (IBD)
  • Psoriasis
  • Noninfectious uveitis (an inflammatory eye disorder without an infection)

There's also a link between TNF and insulin resistance, a condition that leads to type 2 diabetes. Your pancreas makes the hormone insulin to help cells turn blood sugar into energy. If your cells don't respond to the insulin, you have insulin resistance. If you're overweight, your body makes more TNF, which also leads to insulin resistance.

Testing for high TNF alpha

Your doctor may order a tumor necrosis factor alpha blood test to check your levels. If your levels are higher than they should be, it suggests you may have inflammation that's going on longer than it should. 

You could have an infection or a chronic inflammatory disease, such as arthritis. Higher-than-normal TNF-alpha levels in your blood may also help doctors tell how sick you are when you have a serious infection, such as sepsis. It could tell them how you'll do after infection with a viral illness, such as COVID-19, too.

But because TNF alpha is part of your body's general inflammatory response, it can't tell you whether you've got a specific autoimmune or inflammatory condition. Normal levels of TNF alpha also don't mean you don't have a disease. Your doctor will help you understand what your results mean, depending on your symptoms, a physical exam, and any other test results.

Having the right amount of tumor necrosis factor in your body is important. If you're healthy, your body naturally takes care of this. It blocks any extra TNF you might have. That doesn't always happen in diseases like rheumatoid arthritis, so you end up with too much TNF in your blood. When this happens, it leads to inflammation and painful symptoms that don't go away without treatment.

Fortunately, there are drugs that block excess tumor necrosis factor. They're part of a group called biologics, and you might hear your doctor call them one of these names:

  • TNF inhibitors
  • Anti-TNF agents
  • Anti-TNF drugs
  • TNF blockers
  • Anti-tumor necrosis factor

These drugs include:

  • Adalimumab (Humira), adalimumab-atto (Amjevita)
  • Certolizumab pegol (Cimzia)
  • Etanercept (Enbrel), etanercept-szzs (Erelzi)
  • Golimumab (Simponi, Simponi Aria)
  • Infliximab (Remicade), infliximab-dyyb (Inflectra)

These drugs stop TNF's “create inflammation now” message before it can get to other cells. The result is less inflammation in your joints, digestive tract, or skin, depending on what disease you have and where your inflammation is. These medications can be used to treat many conditions, including:

  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Juvenile arthritis
  • Crohn's disease
  • Ulcerative colitis
  • Ankylosing spondylitis
  • Psoriasis

If you have rheumatoid arthritis and don't get better with TNF inhibitors, you may try baricitinib (Olumiant) or tofacitinib (Xeljanz). They are in a class of drugs known as Janus kinase (JAK) inhibitors. JAK inhibitors work by stopping other signals that cause inflammation.

Doctors are studying the effects of a TNF inhibitor on type 2 diabetes, but there are no conclusive results. Some studies show it helps with insulin resistance, but others don't. More work is needed.

What to expect when you take a TNF inhibitor

If your doctor tells you to take a TNF inhibitor, you can pick between two ways. Usually you'll take it as a shot (injection) you'll give yourself with a really small needle at home. You'll put it just under your skin in your belly or thighs. You'll likely take it once every week to every month. The other way you can take it is in an infusion (IV). You'll have to see your doctor to get it this way every month or two. 

Most people who take TNF inhibitors will start to feel better after the first couple of doses. It could take up to 3 months to feel better, but TNF inhibitors can have side effects. Ask your doctor what side effects you should watch for, depending on which medicine you're taking.

The most likely side effect is a skin reaction where you give yourself a shot. These should go away within a week.

It's rare, but some people can have a severe allergy to an IV of a TNF alpha inhibitor. Signs of a severe allergic reaction include:

If you take a TNF inhibitor, you may also be at more risk for:

  • Infections, including tuberculosis (TB) or fungal infections
  • Skin cancer
  • Multiple sclerosis

If you have heart failure and take a TNF inhibitor, it could make your heart condition worse. You shouldn't take a TNF inhibitor if you have a high fever or need antibiotics for an infection. If you need to stop taking your medicine because of an infection, you can start it up again after you get better. Talk to your doctor about any side effects you have or worries you have about possible side effects.

Yes. Get moving. Exercise will help get rid of fat, where TNF lives. And it can help reverse metabolic syndrome, which leads to insulin resistance and type 2 diabetes. The U.S. Department of Health and Human Services suggests that adults get 150 minutes of moderate exercise each week. That's 30 minutes a day, 5 days a week. Take a walk or ride a bike. If you can't do half an hour, do shorter bursts of at least 10 minutes of exercise. Add muscle-strengthening activities at least 2 days a week. Pushups, situps, and weightlifting are options. If you're not used to exercising, start slowly and check with your doctor first.

Though there isn't a specific diet that fights inflammation, you can add these foods to your list:

  • Green, leafy vegetables
  • Fatty fish, like salmon, tuna, sardines, and mackerel
  • Fiber
  • Fruits, like strawberries, blueberries, cherries, and oranges
  • Nuts
  • Olive oil
  • Tomatoes

And avoid these foods

  • Fats like margarine, shortening, and lard
  • Fried foods
  • Red meat and processed meat
  • Refined carbs, like white bread and pasta
  • Soda and sugary drinks

There's some evidence that curcumin found in turmeric can block TNF alpha. Turmeric is the yellow spice used in many curries. It's also considered safe. But more study is needed to know how much to take and whether curcumin can help a lot with diseases related to high TNF alpha levels. 

Scientists also thought an acid found in pomegranates or pomegranate fruit extracts might help with inflammation by blocking inflammation. But a clinical trial didn't show that pomegranate affected the amount of TNF alpha in the blood. It's always a good idea to check with your doctor before taking any new supplements.

TNF is a protein your body needs to cause inflammation that helps protect you against infections and cancer. But too much TNF can lead to chronic inflammation and inflammatory diseases, including various forms of arthritis. If you have an autoimmune or inflammatory disease and high TNF alpha, taking a TNF inhibitor may help to lower your TNF levels and feel better.

  • What does TNF do?

TNF is a cytokine, or chemical messenger. It sends signals to your immune system to protect you against germs, tumors, or other threats. TNF fights those threats by triggering inflammation in your body. When your levels are too high, it also can trigger chronic inflammation and autoimmune or inflammatory diseases.

  • What is the role of TNF in inflammation?

TNF is an important signal that controls inflammation in your body. If your TNF levels are low, you'll have less inflammation. When your levels are high, you'll have more inflammation. Normally, TNF should go up and turn inflammation on when you need it to fight some threat. Once the threat is gone, TNF should go back down. If TNF stays up for a long time when there is no threat, you can have chronic inflammation and many diseases.

  • What immune cells produce TNF alpha?

TNF alpha is made by your white blood cells. More specifically, it's made by macrophages, T lymphocytes, and natural killer cells. All of these immune cells in your blood help your body gobble up, clear away, and fight germs or cancer.

  • What causes TNF release?

Your macrophages and other white blood cells will release TNF alpha quickly after an injury (trauma) or infection. It's one of the first signals in your body any time you have inflammation. Scientists consider it a "master regulator" because it gets the whole inflammatory process going.