IL-8: 53 Ways to Naturally And Artificially Lower This Chemokine

Interleukin 8 (CXCL8)

I decided to write this post because my IL-8 serum levels were elevated @228.8 pg/mL.

 
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Basics

 
 

Interleukin 8 (IL8 or CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. R

IL-8, also known as neutrophil chemotactic factor, has two primary functions: R

  1. It induces chemotaxis in target cells, primarily neutrophils but also other granulocytes, causing them to migrate toward the site of infection.
  2. It also induces phagocytosis once they have arrived.

IL-8 is also known to be a potent promoter of angiogenesis. R

The primary targets of IL-8 are neutrophil granulocytes, endothelial cells, macrophages, mast cells, and keratinocytes. R

IL-8 can be secreted by any cells with toll-like receptors that are involved in the innate immune response. R

IL-8 can also be neuroprotective and help with anxiety in suicidal patients. R

You can test for you IL-8 levels here.

Downsides To Elevated IL-8

 
 

There are many pathologies associated with high IL-8: 

  • Allergic Rhinitis R
  • ALS R 
  • Alzheimer's Disease R
  • Asthma R
  • Atherosclerosis (TNF, IL1b and IL-8 enhance the binding of LDL to blood vessels) R R
  • Behçet's Disease R
  • Cancer (Prostate, Breast, Colorectal Liver, Thyroid, Myeloma) R R R R R
  • Chronic Fatigue Syndrome (esp after an infection) R R
  • Colitis R
  • COPD R
  • Crohn's R
  • Cystic Fibrosis R
  • Eczema R
  • Fibromyalgia R
  • Gingivitis R
  • Heart Disease R
  • IBS R
  • Increased Chance of Offspring Having Schizophrenia (if mother is pregnant with high IL-8) R
  • Lower Chances of Reacting to Anti-Psychotics R
  • Lower Gray Matter in the Hippocampus R
  • Lyme R
  • Migraines R
  • Multiple Sclerosis R
  • Obesity R
  • Oxidative Stress/Inflammation R
  • Osteoperosis (after menopause) R
  • Pain R R
  • Psoriasis R
  • Rheumatoid Arthritis R
  • Sleep Apnea (IL-8 and hypoxia) R
  • Thyroiditis R
  • Vitiligo R

How To Decrease IL-8

 
 

Anything that inhibits NF-kB, IL-1, and TNF-a should theoretically reduce IL-8 also. R R R

Lifestyle/Diet

Supplements

Hormones

Devices/Drugs

  • Angiotensin converting enzyme inhibitors R
  • Aspirin R
  • Artemisinin R
  • Doxycycline R
  • Low-Level Laser Therapy R R
  • Statins R

What Increases IL-8?

 
 

If your IL-8 serum levels are high, its probably better to stay away from these:

  • Exercise (in muscles) R
  • Sun R
  • Smoking R
  • UVA (alpha-tocopherol can prevent the increase of IL-8) R
  • UVB R
  • Lithium R
  • Panax Ginseng R
  • Butyrate R
  • Resistant Starch R
  • Salmonella
  • Oxidative Stress R
  • Obesity R
  • Estradiol R
  • Homocysteine R
  • Angiotensin II R

Mechanism of Action

 
 

IL-8 is initially produced as a precursor peptide of 99 amino acids long which then undergoes cleavage to create several active IL-8 isoforms. R

  • There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2.
  • Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2).
  • Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response.
  • In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca2+, exocytosis (e.g. histamine release), and the respiratory burst. 

Usually, it is the macrophages that see an antigen first, and thus are the first cells to release IL-8 to recruit other cells. R

Both monomer and homodimer forms of IL-8 have been reported to be potent inducers of the chemokine receptors CXCR1 and CXCR2. R

The homodimer is more potent, but methylation of Leu25 can block the activity of homodimers. R

In human keratinocytes, MSK acts predominantly to regulate inflammation via IL-8. R

Expression

The expression of IL-8 is negatively regulated by a number of mechanisms. MiRNA-146a/b-5p indirectly represses IL-8 expression by silencing the expression of IRAK1. R

Additionally, the 3'UTR of IL-8 contains a A/U-rich element that makes it extremely unstable under certain conditions. IL-8 expression is also regulated by the transcription factor NF-κB. R

Genetics

 
 

In humans, the IL-8 protein is encoded by the IL8 gene. R 

IL-8 is a member of the CXC chemokine family. The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q. R R

SNPs

  • rs4073
  • rs2227306
  • rs2227307
  • rs20541
  • rs1800871
  • rs1061170
  • rs2274700
  • rs4253778
  • rs708272
  • rs2230199
  • rs16858811
  • rs1800795
  • rs2243250
  • rs380390
  • rs2234671
  • rs10191411
  • rs1800925
  • rs11536889
  • rs40401
  • rs2070874
  • rs4986790
  • rs2227284
  • rs5882
  • rs6723449
  • rs1008563

More Research

  • Appendicitis patients had lower level of neutrophil DEFA1,3, but higher levels of ALPL and CXCR2/IL8RB. R
  • NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis. R
  • Addition of IL-8 rescued defects in cell migration and invasion observed in ATM-depleted cells thus validating this target. R
  • The production of IL-8 was inhibited by IFN-gamma, and IFN-gamma and IL-4 both completely abrogated the histamine-induced IL-8 production. These results suggest that the histamine-induced IL-6 production and IL-8 production are differentially regulated by IFN-gamma and IL-4. Histamine may be an important modulator of cytokine production in epidermal milieu. R
  • Natural Ways to Inhibit IL-8: A Critical Component of Cancer and Heart Disease R