Eicosanoid – Definition, Function and Significance

What Are Eicosanoids?

Eicosanoids are a group of highly bioactive, lipid-based signaling molecules synthesized by the human body from polyunsaturated fatty acids containing 20 carbon atoms. The name derives from the Greek word eikosi (twenty), referring to this characteristic chain length. Acting as local tissue hormones, eicosanoids typically exert their effects at or near the site of production, regulating a wide range of physiological and pathophysiological processes.

Biosynthesis and Precursor Molecules

The main precursor fatty acids for eicosanoid synthesis are:

• Arachidonic acid (AA) – an omega-6 fatty acid and the most common precursor, primarily yielding pro-inflammatory eicosanoids.
• Eicosapentaenoic acid (EPA) – an omega-3 fatty acid found in fatty fish and fish oil, which produces predominantly anti-inflammatory or neutral eicosanoids.
• Dihomo-gamma-linolenic acid (DGLA) – an omega-6 fatty acid that can also generate anti-inflammatory eicosanoids.

These fatty acids are released from cell membranes by phospholipases (mainly phospholipase A2) and subsequently processed by different enzyme systems.

Classification: Types of Eicosanoids

Depending on the biosynthetic pathway and enzymes involved, eicosanoids are divided into four major classes:

1. Prostaglandins

Prostaglandins are synthesized via the cyclooxygenase pathway (COX-1 and COX-2). They regulate inflammation, pain perception, fever, gastric mucosal protection, and uterine contractions during labor. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin specifically inhibit these enzymes.

2. Thromboxanes

Thromboxanes (especially thromboxane A2) are also produced via the COX pathway and play a central role in blood clotting and platelet aggregation. Excessive thromboxane activity can increase the risk of heart attack and stroke.

3. Leukotrienes

Leukotrienes are formed through the lipoxygenase (LOX) pathway and are particularly important in allergic reactions and bronchial asthma. They promote bronchospasm, increase mucus secretion, and recruit immune cells to inflamed tissue.

4. Lipoxins

Lipoxins are also generated via lipoxygenase enzymes but act predominantly as anti-inflammatory and pro-resolving mediators. They are considered natural counterparts to pro-inflammatory eicosanoids and play an important role in resolving inflammatory responses.

Biological Functions

Eicosanoids fulfill numerous important roles in the body:

• Regulation of inflammation – both initiation and resolution of inflammatory processes
• Pain modulation – sensitization of pain receptors (nociceptors)
• Fever – prostaglandin E2 acts as a central pyrogen in the hypothalamus
• Blood clotting – thromboxane A2 promotes, while prostacyclin (PGI2) inhibits platelet aggregation
• Vascular tone – influencing dilation or constriction of blood vessels
• Immune response – directing immune cell activation and migration
• Reproduction – involvement in ovulation, implantation, and preparation for childbirth
• Kidney function – regulation of renal blood flow and fluid balance

Clinical Significance

An imbalance in eicosanoid production is involved in the development and progression of many chronic diseases, including:

• Chronic inflammatory conditions (e.g., rheumatoid arthritis, inflammatory bowel disease)
• Bronchial asthma and allergic diseases
• Cardiovascular diseases (e.g., atherosclerosis, myocardial infarction)
• Cancer (certain prostaglandins promote tumor growth and metastasis)
• Chronic pain syndromes

Many established medications specifically target eicosanoid signaling pathways. NSAIDs (e.g., ibuprofen, diclofenac) inhibit cyclooxygenase and thereby reduce prostaglandin synthesis. Acetylsalicylic acid (aspirin) irreversibly acetylates COX-1, reducing thromboxane production in platelets. Leukotriene receptor antagonists such as montelukast block leukotriene receptors and are used in asthma management. Corticosteroids inhibit phospholipase A2, suppressing the entire eicosanoid cascade.

Dietary Influence

Diet has a significant impact on eicosanoid balance. A high intake of omega-6 fatty acids (e.g., from sunflower oil and meat) promotes the production of pro-inflammatory eicosanoids derived from arachidonic acid. An abundant intake of omega-3 fatty acids (e.g., from fatty fish, flaxseed oil, and walnuts) shifts the balance toward less pro-inflammatory eicosanoids and may reduce the risk of chronic diseases. The omega-6 to omega-3 ratio in the modern Western diet is often 10:1 to 20:1 – a ratio of approximately 4:1 or lower is generally recommended.

References

1. Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(5):986-1000. doi:10.1161/ATVBAHA.110.207449
2. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochemical Society Transactions. 2017;45(5):1105-1115. doi:10.1042/BST20160474
3. Funk CD. Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology. Science. 2001;294(5548):1871-1875. doi:10.1126/science.294.5548.1871