Tumor Necrosis Factor (TNF) and Inflammation: What’s the Link?

Tumor necrosis factor (TNF) is a type of cytokine. This is a signaling protein made by your white blood cells. Cytokines are released during an immune system response to threats such as tumor cells, viruses, and bacteria.

TNF triggers the inflammatory process to fight threats to your body. However, too much TNF can result in excess inflammation. This is what occurs in autoimmune diseases, conditions in which your body attacks healthy cells and tissues.

This article explains the role of TNF and how it impacts your immune system. It also describes the problems caused by high TNF levels and ways to reduce inflammation.

Tumor Necrosis Factor and Immune System: Role of TNF

Tumor necrosis factor is necessary for a normal immune response. It is a pro-inflammatory agent that helps to regulate inflammation.

Inflammation is the response your immune system creates to an injury, infection, or disease. While the effects of inflammation, such as swelling or fever, may not be pleasant, they work to protect the affected area or body system to allow for healing.

When your body is healthy, it needs only small amounts of TNF so it naturally blocks any excess TNF. When dysfunction causes excess TNF, the unused TNF can trigger inflammation that attacks healthy cells and tissue. This results in autoimmune diseases and other acute and chronic conditions.

Causes of TNF Dysfunction

Causes of TNF dysfunction include infections and other inflammatory stimuli, including aging. Genetics and poor nutrition may also contribute to abnormally high levels of TNF.

TNF dysfunction may also be affected by immune system disorders that include the following:

• AIDS
• Allergies
• Cancer
• Chemotherapy and other cancer-fighting drugs
• Smoking
• Alcohol

Conditions Linked to Increased TNF Production

The overproduction of TNF is linked with chronic inflammation that can lead to complications resulting in a number of autoimmune and inflammatory diseases.

Autoimmune Diseases

Autoimmune diseases occur when your immune system dysfunctions and attacks your body's healthy cells and tissues the same way it treats infections. TNF dysfunction is linked with the following autoimmune diseases:

• Rheumatoid arthritis
• Inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis)
• Psoriasis
• Psoriatic arthritis
• Juvenile idiopathic arthritis
• Ankylosing spondylitis
• Noninfectious uveitis
  

Acute and Chronic Diseases

While TNF can help regulate the factors that fight infectious, elevated levels of TNF are linked with the following diseases:

• Sepsis
• COVID-19
• Human immunodeficiency virus (HIV)
• Chronic obstructive pulmonary disease (COPD)
• Heart failure
  

Metabolic Disorders

Chronic inflammation and elevated levels of TNF are linked with the following metabolic disorders:

• Type 2 diabetes
• Obesity

Medical Treatment: TNF Inhibitors

Medical treatment for TNF dysfunction often involves the use of TNF inhibitors, also called TNF-alpha or TNFα inhibitors or blockers.

TNF inhibitors are biologics (derived from biological sources) that work by neutralizing the activity of TNF. This interferes with the ability of TNF to impact inflammation and the factors that lead to autoimmune diseases.

TNF inhibitors are administered via injection or infusion, depending on the type of drug used. Injectable drugs are self-administered or given by a caregiver with a self-injectable device (like an auto-injector pen) or prefilled syringes. Infusions, given via intravenous (IV; within a vein) injection, are done at a medical office or infusion center.

Types

The five types of TNF inhibitors approved by the Food and Drug Administration (FDA) are:

• Enbrel (etanercept)
• Remicade (infliximab)
• Humira (adalimumab)
• Simponi (golimumab)
• Cimzia (certolizumab pegol)

TNF inhibitors differ in the way they work and the types of autoimmune diseases for which they are indicated. They are used in treating the following diseases in addition to off-label uses:

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

Side Effects

In blocking TNF activity, TNF inhibitors trigger your immune system to shut down the inappropriate immune response. However, this can also result in suppressing the antibodies that protect you against disease. This can leave you susceptible to serious side effects such as a severe infection.

As a result of the increased risk of infection they trigger, TNF inhibitors carry a boxed warning, the strongest warning issued by the FDA. The warnings make patients and providers aware of the following potential side effects:

• Risk of serious infections, such as tuberculosis (TB), pneumonia, sepsis, and osteomyelitis, that may lead to hospitalization or death
• An increased risk of lymphoma and malignancies such as nonmelanoma skin cancer due to an imbalance in antitumor mechanisms
• A rare type of T-cell lymphoma

Due to the increased risk of infection, strict attention to guidelines regarding self-hygiene, infection control, and annual influenza vaccination is necessary when taking TNF inhibitors.

The following minor side effects are linked to TNF inhibitors:

• Headache
• Rash
• Abdominal distress
• Upper respiratory symptoms
• Infusion reactions

Infusion reactions can include:

• Injection site reactions
• Fever
• Hypotension (low blood pressure)
• Shortness of breath
• Urticaria (hives)

Though rare, TNF inhibitors can also trigger the following side effects:

• Demyelinating disorder
• Multiple sclerosis (MS)
• Optic neuritis
• Peripheral demyelinating disease
• Guillain-Barré syndrome (GBS)
  

Other Ways to Lower or Manage Inflammation

In addition to treating the overproduction of TNF with TNF inhibitors, there is evidence that the following strategies can help to lower or manage inflammation:

Follow an Anti-Inflammatory Diet

An anti-inflammatory diet like the Mediterranean diet emphasizes the consumption of whole, unprocessed foods without added sugar while avoiding packaged food, processed red meat, full-fat dairy items, and food with added sugar and salt.

Replace inflammatory foods with the following foods that help fight inflammation:

• Tomatoes
• Olive oil, avocados, and other heart-healthy fats
• Leafy green vegetables like kale, spinach, collard greens, and brussels sprouts
• Plant-based proteins such as nuts, beans, and seeds
• Fatty fish like salmon, tuna, mackerel, and sardines
• Dark, colorful fruits including strawberries, cherries, blueberries, and oranges
• Whole, unprocessed grains
• Fresh herbs and spices including ginger, garlic, and turmeric

Get at Least 20 Minutes of Moderate Exercise Daily

Regular exercise has protective effects against inflammation. Research indicates that one 20-minute session of moderate exercise like fast walking can trigger your immune system to produce an anti-inflammatory response.

Quit Smoking

Smoking promotes chronic inflammation throughout your body. There is evidence that nicotine activates neutrophils (a type of white blood cells) that release molecules that trigger inflammation.

Establish and Maintain a Healthy Weight

Weight loss in overweight and obese people has been identified as a factor for reducing the level of pro-inflammatory markers. Consuming a low-calorie diet can have an anti-inflammatory effect.

Summary

Tumor necrosis factor (TNF) is a type of protein that helps support your body's immune response. It is key to the inflammation process that supports healing when your body is attacked by trauma or disease.

Excess levels of TNF can be harmful. Having too much TNF is linked to autoimmune diseases like IBD and psoriasis.

Long-term drugs called TNF inhibitors work to block the effects of TNF. While they are useful in treating TNF problems, these drugs suppress your immune system. This can raise your risk of infection and other side effects.