Summary of TNF

The three most common inflammatory cytokines that are responsible for chronic inflammatory diseases are Tumor Necrosis Factor (TNF), Interleukin-1beta (IL-1b) and Interleukin-6 (IL-6). 

TNF plays a major role in many diseases, including autoimmune diseases, heart disease, and cancer. TNF increases CRP, which is a common blood measurement to gauge inflammation.

An Introduction to Tumor Necrosis Factor (TNF)

The three most common inflammatory cytokines that are responsible for chronic inflammatory diseases are Tumor Necrosis Factor (TNF), Interleukin-1beta (IL-1b) and Interleukin-6 (IL-6).

TNF can be increased in Th1 or Th2 Dominant?">either Th1 dominance or Th2 dominance. TNF increases CRP, which is a common blood measurement to gauge inflammation.  

TNF is released by Macrophages, Dendritic cells, T cells, Fat cells, and Fibroblasts. TNF then affects various cells. In particular, it will affect cells that line our blood vessels (endothelial cells), which causes vascular problems and this strongly causes cancer, as it causes angiogenesis and increased blood vessel formation (hypervascularization).

It can also cause heart disease, kidney disease, and cognitive problems. TNF negatively affects paneth cells (in the intestine), causing cell death, leaky gut, IBS, and IBD. TNF stimulates macrophages and effector T cells, which leads to more inflammatory cytokine production and apoptosis resistance (which contributes to cancer). See my post on the immune system for a complete understanding.

The Good

TNF induces sleep and it increases non-rem sleep (R). Therefore, it's good to have this elevated somewhat at night when we want to fall asleep. TNF is elevated naturally in healthy people at night time.

The duration of daytime sleep in Alzheimer's disease correlated with the degree of functional impairment in the patient (R), which is a result of elevated inflammation. Other examples of daytime sleepiness in chronic inflammatory states are Parkinsons disease (R), traumatic brain injury (TBI) (R), stroke (R), heart failure (R), and type-2 diabetes (R).

TNF is a direct fat buster, which leads to insulin resistance in fat cells (R), but also insulin resistance in muscle cells (R). This means that glucose can't make its way into these cells.

TNF suppresses appetite by suppressing orexin (RR2R3). So high levels of TNF makes you thinner by causing you to eat less and by inhibiting glucose into fat cells.

If you decrease TNF, you will become more hungry and store more fat. Hence, it's not surprising that anti-TNF therapy results in weight gain -an average of 5.5kg or 11 pounds in only 12 weeks (R).  

The Bad

TNF plays a major role in many diseases and is a cytokine that is a performance killer. TNF can cause lasting harm by damaging your mitochondria (R). TNF makes you tired, lowers your mood and decreases cognitive and physical performance by suppressing orexin (RR2R3).

Orexin is an extremely important neurotransmitter for many bodily functions. Orexin performs a number of key roles in memory acquisition and consolidation, as well as in long-term memory reinforcement (R). Hence, if you have elevated inflammation, it will harm your cognitive performance (also by decreasing BDNF, etc). Read my article on increasing orexin.

TNF can also lower thyroid hormones, causing 'low T3 syndrome' (R). It can also lower testosterone (trended, but not significant) (R). TNF slows wound healing, which means you'll need more time to recover from exercise/injuries. (RR2).

TNF can induce a 'leaky gut' (R). Chronically elevated TNF-alpha can also disturb the circadian rhythm and cause fatigue in the day (R). TNF can keep you from getting into ketosis (R).

When your natural skin fungus gets out of control, the body attacks it with cytokines that include TNF (also IL-6, IL-1b, IL-8), which recruits other aspects of the immune system (R).

Diseases Associated With TNF-alpha

  • Autoimmune disease: in general (R), Multiple Sclerosis (R), Behcet's (R), SLE (R), Scleroderma  (R), Sarcoidosis (R), Hidradenitis suppurativa (R), Ankylosing spondylitis (R), Erythema nodosum leprosum (R)
  • Heart disease (R) - Heart failure (R), Atherosclerosis (R), Stroke (R)
  • Cancer in general (R), Melanoma (R)
  • Insulin Resistance (R), Diabetes II (R)
  • Alzheimer's (R), Parkinson's (R), ALS (R)
  • Major Depression (R) - Depressed people had TNF levels that were about 3.97 pg/ml higher than healthy people (R).
  • IBS (R, R2), Crohn's/Ulcerative Colitis (R)
  • Rheumatoid Arthritis (R)
  • Osteoporosis (R)
  • Psoriasis (R), Eczema (R)
  • Asthma (R), COPD (R). TNF  stimulates various molecules which recruit eosinophils, neutrophils, and lymphocytes to the airway. TNF can induce corticosteroid resistance (R).
  • OCD - only sometimes (R),  Schizophrenia (R), Bipolar (R, R2), Anorexia (R)
  • PCOS (R) - TNF shifts production of cortisol to testosterone, hence causing PCOS (R).
  • Chronic Fatigue Syndrome (R), Fibromyalgia (R) - contradictory (R).
  • Others: Tinnitus (R)Epilepsy (R), Cystic Fibrosis (R), Chemotherapy-induced neuropathy (R), Diabetic Neuropathy (R), Chronic liver disease (R), Fatty Liver (R)

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Protein names

Recommended name:

Tumor necrosis factor

Short name:


Alternative name(s):

Tumor necrosis factor ligand superfamily member 2
N-terminal fragment

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TNF Interacts with These Diseases


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