How Does TNF Cause Inflammation?

Medically Reviewed by Carol DerSarkissian, MD on August 30, 2022

If you have an immune system disease like rheumatoid arthritis (RA), you may have heard your doctor use the term TNF. It's shorthand for tumor necrosis factor, a protein in your body that causes inflammation and helps coordinate the process.

It may surprise you to learn that inflammation can be 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 your immune system is doing its job.

Sometimes, inflammation isn't good for the body. If you have a disease like RA 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.

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. TNF is a major player when it comes to inflammation.

Think of the white blood cells that make tumor necrosis factor as the army. TNF is the signal that tells the rest of the defense units where to go and what to do.

What do these defense units do? 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 unpleasant symptoms:

If you have a lot of TNF but no infection, your immune system may not be working properly. Symptoms are usually different from when you have an infection. 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 RA, they play a role in joint swelling and redness, aka joint inflammation.

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.

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 RA, so you end up with too much TNF in your blood. That leads to inflammation and painful symptoms.

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

The drugs are:

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. These medications can be used to treat:

Rheumatoid arthritis patients who have not responded sufficiently to TNF inhibitors may be prescribed baricitinib (Olumiant) or tofacitinib (Xeljanz). They are a class of drugs known as Janus Kinase Inhibitors. JAKs work by interrupting the signal pathway from inside the cell involved in the inflammation.

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

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 short bursts of at least 10 minutes. Add muscle-strengthening activities at least 2 days a week. Push-ups, sit-ups, and weight lifting are options.

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

Show Sources

American College of Rheumatology: “TNF Inhibitors.”

Institute for Quality and Efficiency in Health Care: “What Is An Inflammation?”

Arthritis Research UK: “The Science Behind the Success of Anti-TNF Therapy.”

Arundathi Jayatilleke, MD, assistant professor, department of medicine, division of rheumatology, Drexel University College of Medicine, Philadelphia.

The Oncologist: “The Molecular Perspective: Tumor Necrosis Factor.”

UpToDate: “Patient education: Rheumatoid arthritis treatment (Beyond the Basics).”

FDA: “Information on Tumor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi).”

Journal of the American Medical Association: “Non–TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial.”

Arthritis Foundation: “Biologics Overview,” “More Fiber, Less Inflammation?”

Journal of Internal Medicine: “Tumour necrosis factor-a in human adipose tissue – from signalling mechanisms to clinical implications.”

American College of Rheumatology: “TNF Inhibitors.”

Journal of Cellular Biochemistry: “Tumor Necrosis Factor‐Alpha: Role in Development of Insulin Resistance and Pathogenesis of Type 2 Diabetes Mellitus.”

U.S. Department of Health and Human Services: “Physical Activity Guidelines for Americans.”

Harvard Health Publishing: “Foods that fight inflammation.”

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