Prostaglandin levels are a marker of inflammation and overall health.
Prostaglandins and thromboxane A2 (TXA2), collectively termed prostanoids, are formed when arachidonic acid (AA), a 20-carbon unsaturated fatty acid, is released from the plasma membrane by phospholipases (PLAs) and metabolized by the sequential actions of prostaglandin G/H synthase, or cyclooxygenase (COX), and respective synthases.
When inflammation occurs in tissues, prostaglandin E2 (PGE2) is generated from arachidonic acid by the enzyme cyclooxygenase-2 (COX-2). PGE2 regulates multiple functions in various immune cells by binding to the downstream receptors EP1, EP2, EP3, and EP4.
There are four principal bioactive prostaglandins generated in vivo: prostaglandin (PG) E2 (PGE2), prostacyclin (PGI2), prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α).They are ubiquitously produced – usually each cell type generates one or two dominant products - and act as autacrine and paracrine lipid mediators to maintain local homeostasis in the body. During an inflammatory response, both the level and the profile of prostaglandin production changes dramatically. Prostaglandin production is generally very low in uninflamed tissues, but increases immediately in acute inflammation prior to the recruitment of leukocytes and the infiltration of immune cells.
PGE2 is one of the most abundant PGs produced in the body. Under physiological conditions, PGE2 is an important mediator of many biological functions, such as regulation of immune responses, blood pressure, gastrointestinal integrity, and fertility.
Dysregulated PGE2 synthesis or degradation has been associated with a wide range of pathological conditions.
In inflammation, PGE2 is of particular interest because it is involved in all processes leading to the classic signs of inflammation: redness, swelling and pain.
Redness and edema result from increased blood flow into the inflamed tissue through PGE2-mediated augmentation of arterial dilatation and increased microvascular permeability. Pain results from the action of PGE2 on peripheral sensory neurons and on central sites within the spinal cord and the brain.
PGE2, binding to different EP receptors, can regulate the function of many cell types including macrophages, dendritic cells and T and B lymphocytes leading to both pro- and anti-inflammatory effects. As pro-inflammatory mediator, PGE2 contributes to the regulation of the cytokine expression profile of dendritic cells (DC)s and has been reported to bias T cell differentiation towards a T helper (Th) 1 or Th2 response.
PGE2 can thus modulate various steps of inflammation in a context-dependent manner and coordinate the whole process in both pro-inflammatory and anti-inflammatory directions. This dual role of PGE2 and its receptors in modulating the inflammatory response has been observed in several disorders. In atherosclerosis, EP4 deficiency promotes macrophage apoptosis and suppresses early atherosclerosis in LDLR−/− mice chimeric for EP4−/− in hematopoietic cells after 8 weeks on a Western diet. EP2 deficiency in hematopoietic cells revealed a trend for similar, but modest, effects on atherosclerosis.
References:
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449. PMID: 21508345; PMCID: PMC3081099.
Friedman EA, Ogletree ML, Haddad EV, Boutaud O. Understanding the role of prostaglandin E2 in regulating human platelet activity in health and disease. Thromb Res. 2015 Sep;136(3):493-503. doi: 10.1016/j.thromres.2015.05.027. Epub 2015 May 28. PMID: 26077962; PMCID: PMC4553088.
Mizuno R, Kawada K, Sakai Y. Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer. Int J Mol Sci. 2019 Dec 11;20(24):6254. doi: 10.3390/ijms20246254. PMID: 31835815; PMCID: PMC6940958.
Tchetina EV, Di Battista JA, Zukor DJ, Antoniou J, Poole AR. Prostaglandin PGE2 at very low concentrations suppresses collagen cleavage in cultured human osteoarthritic articular cartilage: this involves a decrease in expression of proinflammatory genes, collagenases and COL10A1, a gene linked to chondrocyte hypertrophy. Arthritis Res Ther. 2007;9(4):R75. doi: 10.1186/ar2273. PMID: 17683641; PMCID: PMC2206385.
Legler DF, Bruckner M, Uetz-von Allmen E, Krause P. Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol. 2010 Feb;42(2):198-201. doi: 10.1016/j.biocel.2009.09.015. Epub 2009 Sep 27. PMID: 19788928.
Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001 Nov 30;294(5548):1871-5. doi: 10.1126/science.294.5548.1871. PMID: 11729303.
Babaev VR, Chew JD, Ding L, Davis S, Breyer MD, Breyer RM, Oates JA, Fazio S, Linton MF. Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis. Cell Metab. 2008 Dec;8(6):492-501. doi: 10.1016/j.cmet.2008.09.005. PMID: 19041765; PMCID: PMC2614698.
Prostaglandin E2 (PGE2) is a natural chemical your body produces that plays a crucial role in regulating inflammation, pain, blood flow, and body temperature. It acts as a signaling molecule, helping your body respond to injury, infection, and certain hormone changes. PGE2 exerts its effects through specific cell surface receptors (EP1–EP4), which are found throughout the body.
If your PGE2 levels are elevated, it usually means your body is responding to a process that requires attention. Some common reasons for high PGE2 include:
Inflammation: PGE2 increases when your immune system is active, such as in rheumatoid arthritis, inflammatory bowel disease (IBD), or chronic lung conditions. This often leads to symptoms like swelling, redness, and pain.
Pain or Injury: Tissue damage, like that from osteoarthritis, surgery, or injury, can trigger your body to make more PGE2, contributing to pain and tenderness.
Fever or Infection: PGE2 helps regulate body temperature. During infections or inflammatory processes, levels can rise and cause fever and malaise.
Hormone-Related Conditions: PGE2 is involved in hormone regulation and is linked to menstrual cramps, endometriosis, and other hormone-related imbalances, sometimes causing symptoms like heavy bleeding or severe cramps.
Tumors and Rare Syndromes: Certain tumors (such as neural crest tumors or pheochromocytomas) and rare conditions like watery diarrhea syndrome can also cause elevated PGE2.
A high PGE2 level is a clue, not a diagnosis. It indicates that your body is responding to inflammation, pain, hormonal changes, or other stressors. Medications like nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce PGE2 and help with symptoms, but it’s important to work with your healthcare provider to identify and address the underlying cause. Persistent symptoms or unexplained high PGE2 should prompt further medical evaluation.
| Cause/Condition | Example Disorders | Common Symptoms/Effects |
|---|---|---|
| Inflammation | Rheumatoid arthritis, IBD | Swelling, pain, redness |
| Pain or Injury | Osteoarthritis, post-surgery, trauma | Pain, tenderness |
| Fever/Infection | Viral or bacterial infections | Fever, malaise |
| Hormonal Conditions | Menstrual cramps, endometriosis | Cramps, heavy bleeding |
| Tumors/Syndromes | Neural crest tumors, watery diarrhea syndrome | Diarrhea, hormonal symptoms |
In summary: Elevated PGE2 is a sign that your body is reacting to something—most commonly inflammation, injury, infection, or hormonal changes. It’s important to discuss high PGE2 results with your doctor to determine the next steps and appropriate treatment.
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Prostaglandin E2 (PGE2) is a type of chemical messenger (a hormone-like substance) that is involved in various physiological processes in the body, including inflammation, pain, and regulation of blood flow. PGE2 is produced by the body in response to various stimuli and is known to have both pro-inflammatory and anti-inflammatory effects, depending on the context in which it is produced.
A low level of prostaglandin E2 may indicate a decrease in its production or activity in the body. This can have several potential implications, depending on the specific context and location where PGE2 is affected. Some possible causes of low PGE2 levels include certain medications that inhibit PGE2 synthesis (such as nonsteroidal anti-inflammatory drugs or NSAIDs), genetic conditions that affect the production of PGE2, or certain diseases or conditions that disrupt normal physiological processes involving PGE2.
It's important to note that interpreting the meaning of low PGE2 levels would require a thorough evaluation of an individual's specific medical history, symptoms, and other relevant factors by a qualified healthcare professional. They would be able to provide a more accurate and personalized assessment of the implications of low PGE2 levels based on the individual's unique circumstances.
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Optimal Result:
200 - 400 pg/mL.