Summary of IL1B
The IL1B gene codes for interleukin 1-beta (IL-1b). IL-1b is an important inflammatory immune messenger (cytokine). It’s released from white blood cells in response to cell stress, cell damage, or cell death [R, R, R, R].
IL1B variants are linked to many conditions, including:
- Autoimmune disorders, such as rheumatoid arthritis and IBD [R, R]
- Inflammation of the pancreas (pancreatitis) [R]
- Cancer [R]
- Severe inflammatory response to infectious diseases [R]
- Heart disease [R, R]
Recommended name:Interleukin-1 beta
Alternative name(s):IL-1 beta
Top Gene-Substance Interactions
IL1B Interacts with These Diseases
Top Choices To Decrease IL-1beta
Top Functional Foods/Condiments
- Cod liver/Fish oil/DHA (R)
- Jasmine Tea/Tea Polyphenols (R)
- Kombucha/Lactic acid (R)
- Black Cumin Seed Oil (R)...not bad (R)
- Cinnamon/Sodium Benzoate (R)
- Raw honey (R)
- Stevia (R, R2)
- Golden berries (R)
- Trehalose (R, R2)
Top Devices and Lifestyle
Top Supplements to Inhibit IL-1b
- Andrographis (R) - Out of 20 plants, Andrographis inhibited IL-1b the most and was more potent than dexamethasone.
- PQQ (R)
- Fisetin (R)
- Gynostemma (R)
- Curcumin (R) - Powerful suppression in response to IMQ (R)
- Trans-Resveratrol 500mg +5g Leucine (R, R2)
- Luteolin (R)
- EGCG (R) - Powerful (R)
- Apigenin (R)
- Boswellia (R)
- Hydroxytyrosol (R) (not potent)
- Pterostilbene (R) (Strong...30uM)
- Reishi (R) - Powerful
- L Plantarum (R) - for the gut especially.
Foods To Decrease IL-1beta
In general, vegetables and fruit should help decrease IL-1b.
- Cyanidin-3-O-²-glucoside (C3G) - typical anthocyanin (R) - Found in many fruits.
- Ginger (R) - Has lectins, but was one of the most potent out of 20 medicinal plants (R).
- Sulforaphane/Broccoli sprouts/Cruciferous Vegetables (R).
- Anthocyanins (from red raspberries) (R)
- Oat polyphenols (R)
- Astaxanthin in fish (R)
- Betalain/Beets (R)
Other IL-1beta Inhibitors
- Bile (R)
- Vitamin A/Retinol (R)
- B-glucans (R)
- MDMA (Drug) (R) - USE RESPONSIBLY and dose correctly. I'm on the fence with recommending MDMA because you don't know what you're getting. MDMA decreases the amount of IL-beta , which is why you can party on it all night without feeling fatigue. If you took a quarter of the dosage in the daytime, this would be a more responsible way to take this drug. But there's still the variability in quality.
- Autophagy - The natural breaking down of what is unnecessary in the body (R).
- Tart Cherry Extract(R)
- Sialic Acid (R)
- Berberine (R)
- Grape Seed Extract (R)
- Chinese Skullcap/Baicalin (R, R2)
- Ashwagandha (IL-1)
- Slippery elm (R)
- Rhodiola (R)
- Silymarin (R)
- Astragalus (R)
- Rosmarinic acid (R)
- Danshen/Salvia Miltiorrhiza (R)
- Magnolol (R)
- Echinacea (R), Cichoric acid (from Echinacea) (R)
- Mannose? (R)
- Rhubarb/Emodin (found in Resveratrol pills, Rhubarb, Aloe) (R)
- Atractylodes/Atractylenolide I (IL-1)
- Zinc (if deficient) (R)
- Alfalfa (R)
- Perilla (R), Rapamycin - longevity drug (R), Electroacupuncture (IL-1) (R), Mizolastine (antihistamine) (IL-1) (R), Canakinumab (drug) (R).
- Pathways: PPARy (IL-1a) (R), ACE inhibitors (IL-1) (R).
Hormones That Inhibit IL-1b
- a-MSH (R) - Also lessens the stimulatory effects of IL-1b on the HPA axis (R).
- ACTH (R)
- Testosterone (R)
- Ghrelin (R)
What to Avoid: IL-1beta Increasers
- Sleep deprivation (R)
- Smoking (R)
- Excessive glucose (R)
- Alcohol (R)
- Zinc deficiency (R)
- Aldosterone (R, R2) - From ingesting too much salt (R)
- Exercise (R, R2, R3) - But only shortly after. Increased in muscle cells in the long term.
- Melatonin (R) (IL-1)
- Vitamin C deficiency (R)
- Goji Berries (R)
- Lithium (R)
- Aloe - in cancer cells (R), Cat's Claw (R), Grape powder - in response to LPS (R), Agmatine, Mannose Binding Lectin (R)
- S Boulardii (R) and Bacillus Subtilis (R).
IL-1b can become elevated in response to various infections. For example, people with lingering symptoms from Lyme have elevated IL-1b (R).
- Selenium (R)
Substances That Increase IL1B
Substances That Decrease IL1B
Introduction to Interleukin-1 (IL-1)
Twenty-five years ago, immunologists and neuroscientists had fewer science of mutual interest. This is no longer the case. Neuroscientists now know that cytokines like IL-1 interact with neurons of the hypothalamus in many ways (by suppressing orexin, etc..) (R).
Macrophages and a bunch of immune cells produce and release IL-1b and TNF (R). Both are usually elevated together because each increases the other (R, R2), so it's hard to tease out what plays a more significant role.
IL-1beta seems to be the most significant in relation to disease and there's more research on it because it possesses a strong pro-inflammatory effect. If IL-1 is at significantly high levels, it causes fever, increased pain sensitivity, vasodilation, and hypotension (R).
I had the latter 3, but not so much of fever. This cytokine has a natural antagonist, which counteracts its effect - IL-1Ra (IL-1 receptor antagonist) (R). IL-1 can be elevated in either Th1 or Th2 dominance (R).
Fibrinogen (causes clotting) and CRP are increased by IL-1b (R), but these aren't usually elevated unless your cytokines are acutely increased. IL-1b is necessary for replicating Th17 immune cells (R). It also increases nitric oxide and PGE2 (R).
IL-1b will stimulate your HPA axis and sympathetic nervous system, which both go on to lower other cytokines like TNF (R). Like everything else, baseline IL-1b production and production in response to stimuli is genetic. The SNP rs16944 is a polymorphism in the interleukin 1, beta gene and different versions of it are associated with higher and lower risks of various diseases.
It's important to realize that you can have IL-1b elevated locally in areas such as your hypothalamus or gut and it wouldn't show on blood tests. You can check your Interleukin-1beta levels by clicking on the link. You should check this after meals or an autoimmune flair-up.
IL-1b is part of the mechanism of inducing sleep and increases non-rem sleep and the time it takes to fall asleep (R, R2). It works in part by increasing adenosine (R). Therefore, this is not something you want to inhibit during the night. In rodents, IL-1b increased the release of oxytocin and vasopressin (R).
Oxytocin is usually 'good'. IL-1b increases NGF (R). NGF, along with NT-3, are somewhat unique in stimulating neurite growth, which can't be done by NGF, BDNF or NT-4 alone (R). IL-1b also increases GDNF (R), which again stimulates neurite outgrowth.
My advice is to allow this effect when you are supposed to have it: while you're asleep. While my mind worked better in some limited ways with inflammation, it's overall much better now. IL-1b can also increase the release of dopamine, norepinephrine, and serotonin in the frontal part of the hypothalamus (R). (don't know if this is good)
Even a relatively low level of IL-1 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. IL-1beta, however, actually increased aldosterone synthesis by a bit.
I suspect that I used to have low aldosterone, which manifested itself as low blood pressure and exercise headaches/hyponatremia. I believe this was because of the inflammation I was experiencing.
Exercise increases ACTH, which normally tells our body to conserve salt by 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, causing hyponatremia.
The Bad: IL-1 And Performance
I spoke about how trying to increase our motivation or mood by hacks, tricks or by changing our mindset will only increase our neuroticism and delays acceptance of our present reality. However, I support trying to modulate these factors by biological manipulation.
If you have elevated IL-1 then that will affect your mood, cognitive function, levels of wakefulness and motivation and lowering the chronic inflammation is what you need to be focusing on.
IL-1 plays a major role in many diseases and is a cytokine that is a performance killer. It does this in part by inhibiting orexin, which is a central regulator of many bodily functions, but also by many other pathways.
For example, depression can be caused by IL-1 (R, R2), and it may be the cause of your bad moods. IL-1b decreases synthesis of estrogen and increases the breakdown of progesterone (R), both of which are anti-anxiety hormones (R, R2).
IL-1 also harms cognitive performance. IL-1b is detrimental to neuronal synapses during activation-induced inflammation and causes neurodegeneration (R). It can also negatively impact Long Term Potentiation (R), which is critical for learning and memory (R). My memory and cognitive function has improved as I lowered this cytokine in myself.
A significant mechanism in these effects is likely decreased Brain Derived Neurotrophic Factor (BDNF), which is inhibited by IL-1b (at least its end products like CREB). (R) IL-1 also causes fatigue by suppressing orexin (R), and I did experience this. IL-1beta has also implicated in Anxiety and HPA activation (R, R2, R3), IBS (R) (which may include excessive gas), Cognitive deficits (R), and a host of chronic diseases.
Orexin performs a number of key roles in memory acquisition and consolidation, as well as in long-term potentiation (R). Hence, if you have elevated inflammation it will harm your cognitive performance (also by decreasing BDNF, etc). Read my article on increasing orexin .
Studies have found that higher levels of IL-1b are correlated with lower levels of testosterone (R), which helps explain why most people who I consult with that have inflammation also have low testosterone.
Testosterone is a significant performance enhancer. IL-1b can also decrease performance by decreasing the enzymes needed to make Thyroid hormones (T3) and by decreasing the receptors needed for it to function (R, R2). And, indeed, many people with inflammation show lower levels of T3 .
Cortisol also causes lower testosterone (R), but elevated IL-1 causes the release of cortisol to decrease this inflammation (R). So it's hard to know if IL-1 is causing lower testosterone directly or by way of increasing cortisol .
It could be both. IL-1b inhibits insulin release in response to glucose, probably as a result of increased levels of nitric oxide (R). This leads to higher blood glucose levels, which can cause a bunch of downstream negative effects.
Some Significant Factors That Lead to Elevated IL-1b
Lectin sensitivity probably increases IL-1b in the same way that it can increase TNF (R) since these cytokines usually go together. Fat cells produce IL-1beta, so obesity will result in elevated markers of IL-1b (R). Your weight may be causing your performance to decline. IL-1beta is increased by Sleep deprivation (R), Smoking (R), Excessive glucose/sugar (R), and Alcohol (R). Acute exercise also causes a brief spike in IL-1b (a few hours) (R) and TNF-alpha (peaked at 14 min) (R), although this is still beneficial. I notice I get a bit fatigued after push-ups/pull-ups for a short period and this is probably why. Acute psychological stress suppresses TNF-alpha and IL-b and therefore causes wakefulness (R). Sun/UV raises IL-1b, which suppresses orexin . This explains why we get tired if we get too much sun (R). I still recommend the sun because it probably down-regulates (decreases) IL-1 production in the long term. Moderate hypoxia (low oxygen levels) enhances IL-1b production in Macrophages (R).
Random Interesting Information on IL-1beta
IL-1b has a circadian rhythm and is elevated before bed, but if you're a night shift worker, it's shifted to the day time (R). IL-1 does play a role in memory function, so you want some level of it, but as low as possible (R). Increased free fatty acids increase IL-1Ra, leading to decreased fatigue (R). Maybe this is why some people on a high fat diet feel a bit better. Excessive glucose intake causes Insulin Resistance by increasing IL-1b (R).
When your natural skin fungus gets out of control the body attacks it with cytokines that include IL-1b (also IL-6 , TNF , IL-8 ), which recruits other aspects of the immune system (R). The resulting inflammation causes skin reddening or other symptoms.
With regard to inducing fatigue, there are two sides to the picture. IL-1 also increases wakefulness-promoting neurotransmitters to balance out the sleep inducing effects - maintaining homeostasis. It activates Brainstem noradrenergic neurons of the locus coeruleus, dopaminergic neurons of the substantia nigra and ventral tegmental area and histaminergic neurons in the posterior hypothalamus, which are all wakefulness-promoting (R). However, keep in mind these are to counteract the sleep-inducing effects.
Diseases Associated With IL-1b
Realize that these diseases aren't only caused by IL-1b and that not everyone with these diseases has elevated IL-1b . However, these diseases are correlated with IL-1b and the role is usually most likely causal. Also, IL-1b can be more elevated in some tissues compared to others.
- Anxiety and HPA activation (R, R2), (antagonized by MSH (R))
- IBS (R) (excessive gas), Colitis (R)
- Cognitive deficits (R)
- Heart disease (R)
- Depression (R)
- Type 2 diabetes mellitus (R)
- Insulin Resistance (R)
- Cancer in general (R) - Including Oral Cancer (R), Colon Cancer (R), Multiple Myeloma (R), Breast cancer (R)
- Acne (R) (IL-1a)
- Gout (R, R2)
- Migraines (R) (IL-1b increases cox-2 and CGRP release)
- Psoriasis (R), Eczema (R)
- Arthritis (R) - Not as significant as the association with TNF .
- Alzheimer's (R) (Both damaging and healing). Increases amyloid (R).
- Parkinson's (R)
- Schizophrenia (R)
- Multiple Sclerosis (R)
- Osteoporosis (postmenopausal) (R)
- Alcohol-related liver disease (R), Chronic liver disease (R), Tinnitus (R), PCOS (R), Delirium (R)
- Diabetic neuropathy (R), Chemotherapy-induced neuropathy (R)
- Pain hypersensitivity (R)
- Behcet's (R), Lupus -SLE (R)
- UV-induced skin damage (R), Contact allergic dermatitis (R)
- Familial Mediterranean Fever (R), Juvenile Idiopathic Arthritis (R), Endometriosis (R), Anorexia Nervosa (R) - contradictory (R)
Elevated IL-1 and Chronic Infection
Its possible IL-1 is activated by a chronic infection. An infection can also cause Lectin Sensitivity. Many herbs should help here, but in some instances, antibiotics are more useful. Antibiotics like doxycycline should be explored as a last resort. While Doxycycline may not work and may have some side effects, at least it has some potential benefits.
Doxycycline is a nootropic, so it increases the creation of new brain cells and reduces microglia in the hippocampus (memory center) (R) and has been found to extend worm lifespans (R). Minocycline also increases the creation of new brain cells in adults (R) and lifespan in flies (R).
Disclaimer and Caveats
Conditions with Increased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
Conditions with Decreased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
The following transcription factors affect gene expression:
Expressed in activated monocytes/macrophages (at protein level).
- Rheumatoid arthritis
- Immune System
- Cytokine-cytokine receptor interaction
- Chagas disease (American trypanosomiasis)
- Prion diseases
- Toll-like receptor signaling pathway
- Hematopoietic cell lineage
- Type I diabetes mellitus
- Graft-versus-host disease
- Alzheimer's disease
- Osteoclast differentiation
- NOD-like receptor signaling pathway
- MAPK signaling pathway
- Cytosolic DNA-sensing pathway
- African trypanosomiasis
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Mapk Cascade
- Activation Of Mapk Activity
- Fever Generation
- Response To Hypoxia
- Positive Regulation Of Protein Phosphorylation
- Chronic Inflammatory Response To Antigenic Stimulus
- Positive Regulation Of T Cell Mediated Immunity
- Purine Nucleobase Metabolic Process
- Apoptotic Process
- Inflammatory Response
- Immune Response
- Signal Transduction
- Positive Regulation Of Cytosolic Calcium Ion Concentration
- Cell-Cell Signaling
- Embryo Implantation
- Estrogen Metabolic Process
- Negative Regulation Of Cell Proliferation
- Glycoprotein Metabolic Process
- Response To Heat
- Response To Carbohydrate
- Response To Ozone
- Response To Gamma Radiation
- Positive Regulation Of Vascular Endothelial Growth Factor Production
- Positive Regulation Of Gene Expression
- Negative Regulation Of Glucose Transport
- Negative Regulation Of Glutamate Secretion
- Smooth Muscle Adaptation
- Cytokine-Mediated Signaling Pathway
- Pentacyclic Triterpenoid Metabolic Process
- Hyaluronan Biosynthetic Process
- Neutrophil Chemotaxis
- Sequestering Of Triglyceride
- Positive Regulation Of Vascular Endothelial Growth Factor Receptor Signaling Pathway
- Positive Regulation Of Fever Generation
- Lipopolysaccharide-Mediated Signaling Pathway
- Positive Regulation Of Prostaglandin Secretion
- Response To Estradiol
- Interleukin-1 Beta Production
- Positive Regulation Of Granulocyte Macrophage Colony-Stimulating Factor Production
- Positive Regulation Of Interferon-Gamma Production
- Positive Regulation Of Interleukin-6 Production
- Positive Regulation Of Interleukin-8 Production
- Positive Regulation Of Immature T Cell Proliferation In Thymus
- Positive Regulation Of Histone Phosphorylation
- Response To Atp
- Response To Vitamin D
- Response To L-Ascorbic Acid
- Positive Regulation Of Heterotypic Cell-Cell Adhesion
- Positive Regulation Of Histone Acetylation
- Social Behavior
- Ectopic Germ Cell Programmed Cell Death
- Positive Regulation Of Myosin Light Chain Kinase Activity
- Response To Stilbenoid
- Wound Healing
- Positive Regulation Of T Cell Proliferation
- Positive Regulation Of Nf-Kappab Import Into Nucleus
- Positive Regulation Of Apoptotic Process
- Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Response To Morphine
- Negative Regulation Of Map Kinase Activity
- Response To Peptide Hormone
- Protein Kinase B Signaling
- Positive Regulation Of Jun Kinase Activity
- Positive Regulation Of Chemokine Biosynthetic Process
- Positive Regulation Of Interleukin-2 Biosynthetic Process
- Positive Regulation Of Interleukin-6 Biosynthetic Process
- Positive Regulation Of Nitric Oxide Biosynthetic Process
- Response To Ethanol
- Negative Regulation Of Neuron Differentiation
- Positive Regulation Of Angiogenesis
- Negative Regulation Of Lipid Metabolic Process
- Positive Regulation Of Mitotic Nuclear Division
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Jnk Cascade
- Negative Regulation Of Insulin Receptor Signaling Pathway
- Positive Regulation Of Protein Export From Nucleus
- Positive Regulation Of Astrocyte Differentiation
- Positive Regulation Of Phagocytosis
- Regulation Of Insulin Secretion
- Negative Regulation Of Lipid Catabolic Process
- Positive Regulation Of Lipid Catabolic Process
- Regulation Of Nitric-Oxide Synthase Activity
- Positive Regulation Of Membrane Protein Ectodomain Proteolysis
- Positive Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Positive Regulation Of Cell Division
- Positive Regulation Of Cell Adhesion Molecule Production
- Positive Regulation Of Calcidiol 1-Monooxygenase Activity
- Negative Regulation Of Adiponectin Secretion
- Positive Regulation Of Erk1 And Erk2 Cascade
- Monocyte Aggregation
- Cellular Response To Antibiotic
- Cellular Response To Mechanical Stimulus
- Cellular Response To Organic Substance
- Cellular Response To Glucose Stimulus
- Cellular Response To Fatty Acid
- Cellular Response To Organic Cyclic Compound
- Response To Dexamethasone
- Positive Regulation Of Monocyte Chemotactic Protein-1 Production
- Positive Regulation Of Neutrophil Chemotaxis
- Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand
- Regulation Of Establishment Of Endothelial Barrier
- Negative Regulation Of Branching Morphogenesis Of A Nerve
- Negative Regulation Of Neural Precursor Cell Proliferation
- Positive Regulation Of Interleukin-6 Secretion
- Negative Regulation Of Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand