Eicosanoids (Local hormones) - Cell's "First Response" team - Mediators of inflammation / pain, blood pressure, blood clotting, tissue repair . . .

So - Exactly what are eicosanoids?

You may as well know their name, since these vital "local hormones" CAN CHANGE YOUR LIFE

Eicosanoids act as hormones in a cell's local "neighborhood"

These vital chemical mediators are produced when a cell is activated by certain stimuli.      Eicosanoids inform the neighborhood cells of a need to take appropriately balanced action in response to any trauma (e.g. damage, infection, allergens or numerous other intracellular and extracellular stimuli). Example actions include promoting or reducing:

•   Inflammation and related pain, blood flow and body temperature;

•   Immune system response to adverse stimuli, such as allergies, infection, trauma

•   Blood pressure

•   Blood clotting

•   Constrict/dilate blood vessels

•   Smooth muscle contraction / relaxation (incl. vascular, gastrointestinal, uterine and pulmonary)

•   Reproduction and respiratory processes

•  Gastric mucosa protection

•  Cell proliferation / cancer development

•  Accumulating evidence suggests an eicosanoid role in skeletal muscle pain/inflammation, building and repair. 

Unlike the endocrine hormones which act systemically via the bloodstream, eicosanoids work close to their site of production, are short-lived, and usually impact the cell of origin (i.e. operate as autocrine signaling molecules) or pass messages to impact nearby cells (paracrine signaling).

Where do eicosanoids come from?

Long-chain polyunsaturated fatty acids (PUFAs) are the main constituents of our cell membranes. 

Stimulated / induced by physiologic events.   The enzyme phospholipase A2 cleaves 20-carbon-chain PUFAs,  omega-6 AA and DGLA and/or omega-3 EPA fatty acids, from glycerol in the phospholipid bi-layer of the cell membrane, allowing COX and LOX enzymes to convert these freed fattty acids to eicosanoids.   An eicosanoid is named from the Greek eico meaning 20, since it originates from these essential polyunsaturated fatty acids containing 20-carbons in their body.   The "essential" means they must come from diet or supplements because your body can not make them.

Released essential fats are converted to eicosonoids via the COX and LOX enzymes.    Prostanoids (prostaglandins and thromboxanes) from COX-1 and COX-2, and leukotrienes from the LOX enzyme.

COX-1 is always there "quietly" doing housekeeping, but COX-2 is induced "in force" when stimulated.   COX-1 is always present in small amounts in tissues maintaining homestasis, while COX-2 is induced in large amounts after illness /infection /tissue damage (e.g. by trans fats in solvent-expressed vegetable oils) /allergies /air-pollution occur  by appropriate signaling molecules  (e.g. cytokines, tumor promoters and growth factors), and therefore produces comparatively more eicosanoids than COX-1.  Also the  eicosanoids produced by COX-2 tend to be more inflammatory, vasoconstrictive, increase blood clotting, immune suppressive . . . as you will see in:

Chart of Effects of Significant Eicosanoids

Balanced presence of eicosanoid-producing membrane fatty acids is key to health

Each  cell is able to control an appropriately balanced response to outside stimuli by having a balanced presence of fatty acids in the cell membrane, which are released to produce both the inflammatory and anti-inflammatory eicosanoids.   This balance is achieved as the fatty acids compete for the same enzymes for their release from cell membranes (PLA2) and metabolism to eicosanoids (COX-1, COX-2, 5-LOX).

Omega-6 DGLA and omega-3 EPA produce anti-inflammatory  eicosanoids. (Omega-6 DGLA can also metabolize to AA, especially with insufficient EPA present).   

Omega-6 AA produces mostly inflammatory  eicosanoids.

Inflammation is a normally well-regulated, rapidly resolving mechanism to deal with infection or damage to the host, initiating pathogen removal and tissue repair processes. The self-regulated, homeostatic response involves the activation of negative feedback mechanisms, such as:

Secretion of anti-inflammatory mediators

Inhibition of pro-inflammatory signaling cascades and reduction of receptors for inflammatory mediators

Activation of regulatory cells.

•;   Pathological inflammation involves a loss of regulatory processes, which to excess, can cause irreparable damage to host tissues, with potential disease. Irrespective of the cause of the inflammation, the response involves increased blood supply and capillary permeability (permits larger than usual molecules,  to traverse the vasculatory endothelium for delivery of leukocytes (WBCs) to inflammation site). 

Release of mediators from leukocytes at the site of inflammation. These may include lipid mediators (e.g., prostaglandins (PGs), leukotrienes (LTs)), peptide mediators (e.g., cytokines), reactive oxygen species (e.g., superoxide), amino acid derivatives (e.g., histamine), and enzymes (e.g., matrix proteases) depending upon the cell type involved, the nature of the inflammatory stimulus, the anatomical site involved, and the stage during the inflammatory response.  Several of these mediators may act to amplify the inflammatory process acting, for example, as chemoattractants. Some of the inflammatory mediators may escape the inflammatory site into the circulation and from there they can exert systemic effects. For example, the cytokine interleukin (IL)-6 induces hepatic synthesis of the acute phase protein C-reactive protein, while the cytokine tumour necrosis factor (TNF)-α elicits metabolic effects within skeletal muscle, adipose tissue and bone.

Traditional diets typically contained a 1:1 balance of omega-6 and omega-3, which in the common Western diet is now over10:1 as a result of omega-6 linoleic acid (LA) being the most highly consumed polyunsaturated fatty acid, about half of which ???? is eventually converted to AA. Demmelmair et al, 2001 .  

Where are the eicosanoid-producing membrane fatty acids coming from?

Arachidonic acid (AA) (predominately inflammatory)

Estimated adult intake of AA in advanced countries is 100-250mg / day.  Kawashima, 2019

The consumption of dietary vegetable oils provides LA from which cell membrane AA can be derived, but there is a limit to how much LA is converted.   Yes, the main source of omega-6 in the Western diet is indeed Linoleic Acid (LA) from vegetable seed oils, but fortunately, the body has in-built controls that determine how many of these LAs are converted to AA's. This seems to be achieved by down-regulating the Δ6D enzyme, which converts LA to GLA. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review

Plants contain little to no AA.

The major source of dietary AA is MEAT and EGGS.    And notice that dairy is not in the top dozen sources. Whereas human milk is a significant source of AA, cow's milk is not. Also, it is worth mentioning that meat from grass-fed animals and eggs from pastured hens will likely contain less AA than grain-fed animals/birds, since they ate less LA.

Based on data from the National Health and Nutrition Examination Survey 2005-2006 . Percentages rounded off.

Anti-inflammatory DGLA (most potent anti-inflammatory EFA)

In mother's milk.

GLA (which the body can convert to DGLA) can be supplemented in borage, blackcurrant and evening primrose oils:

Borage, blackcurrant and evening primrose oils for DGLA

Anti-inflammatory EPA

Fish oil supplements are becoming a common (and necessary) source of EPA (and DHA)