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). These are the most commonly talked about cytokines in the literature.

The transcription factor nuclear factor NF-kappaB is also heavily spoken about and these four proteins are what people most likely refer to when they talk about chronic inflammation (whether they are aware of this or not).

TNF can be increased in either Th1 dominance or Th2 dominance.

TNF increases CRP, which is a common blood measurement to gauge inflammation.  However, CRP is not sensitive enough to detect lower, but chronic levels of TNF.  See my discussion of this in my IL-6 post.

It’s important to realize that you can have TNF elevated locally in areas such as your hypothalamus or gut and it wouldn’t show on blood tests.

Many kinds of cells release TNF and then TNF goes on to stimulate other immune cells.

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 intestinal cells, 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).

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 Parkinson’s 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 glucosecan’t make its way into these cells.

TNF suppresses appetite by suppressing orexin (R, R2, R3).

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).  It’s incredible that only one variable changed (TNF) and the study participants gained on average 11 pounds.

Low doses of TNF given to mice caused insulin and leptin resistance in the hypothalamus, which should contribute to obesity (R).

Even a relatively low level of TNF decreases aldosterone synthesis in response to ACTH (precursor of cortisol), which increases in response to stress and intense exercise (R). This can lower blood pressure.

Exercise increases ACTH, which normally tells our body to conserve saltby increasing aldosterone. However, if we have inflammation, then aldosterone production will be limited and if we sweat a lot it can cause low levels of salt in the body.

The Bad

I have already spoken about how I think trying to increase your motivation or mood by hacks, tricks, or by changing your mindset will only increase your neuroticism.

If you have elevated TNF and you bring it down, this will positively affect your mood and motivation.

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 (R, R2, R3).

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).

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. (R, R2).

TNF can induce a ‘leaky gut’ (R).

Chronically elevated TNF-alpha can also disturb the circadian rhythmand 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 nodosumleprosum (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)

The Most Significant Factors That Influence TNF

The two main factors that cause elevated TNF, if I had to guess, are lectins(R) and obesity (R), since fat cells produce TNF. If we ate less, a lot of people’s inflammation problems would disappear.

Other likely causes are sleep deprivation (R) and high blood glucoselevels (R) from eating too much, especially high glycemic index foods.

Other common factors are a lack of exercise (R), excess alcohol (R), smoking (R), and not enough fruits and veggies (R, R2).

UV acutely increases TNF (R, R2, R3) (but eventually downregulates it). This is the likely reason why some people experience fatigue from sunbathing.

Recent research indicates that TNF is potently inhibited by exercise (specifically, myokines or proteins produced by the muscles such as IL-6) (R). However, excessive exercise or Marathons will elevate TNF (R).

An infection can also elevate TNF. Bacterial (rather than viral) infections are more likely if you have elevated TNF (R).

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