Eicosanoids are signaling molecules derived from fatty acids that regulate the body’s physiological and pathological processes. They are not stored but are synthesized on demand in response to stimuli like injury or infection. As local hormones, they act near their site of production, influencing nearby cells. This localized action allows for precise control over bodily functions, including immune responses and blood pressure regulation.
Principal Physiological Actions of Eicosanoids
Eicosanoids are central to the inflammatory response, a protective mechanism to remove harmful stimuli and begin healing. Prostaglandins cause blood vessels to dilate, increasing blood flow to an affected area, while leukotrienes make capillaries more permeable. This allows immune cells to move from the bloodstream into the tissue to combat pathogens or clear debris. Leukotrienes also act as chemical signals, guiding these white blood cells to the site of injury or infection.
These molecules are also involved in pain and fever. Prostaglandins can sensitize nerve endings, making them more responsive to pain stimuli. They can also act on the hypothalamus in the brain to raise body temperature, resulting in fever as part of the systemic response to infection.
The regulation of blood clotting is another function, with different types having opposing effects. Thromboxane A2 causes platelets to aggregate and blood vessels to constrict, which are steps for forming a blood clot. In contrast, prostacyclin (PGI2) has the opposite effect, inhibiting platelet aggregation and dilating blood vessels. This balance ensures that blood clots form when needed but do not obstruct blood flow.
Eicosanoids also regulate the contraction of smooth muscles. In the respiratory system, leukotrienes constrict airway muscles, and their overproduction can contribute to asthma symptoms. In the uterus, prostaglandins stimulate the muscle contractions required for childbirth. By influencing smooth muscle in blood vessel walls, eicosanoids help control blood pressure and regional blood flow.
The Synthesis Pathway of Eicosanoids
The production of eicosanoids begins with the release of a 20-carbon polyunsaturated fatty acid from cell membrane phospholipids. The most common precursor is arachidonic acid (AA), an omega-6 fatty acid. This release is triggered by various physical, chemical, or hormonal stimuli, making the fatty acid available for conversion. The enzymatic pathway used determines the type of eicosanoid produced.
Two primary enzymatic pathways convert arachidonic acid into eicosanoids. The cyclooxygenase (COX) pathway uses the COX-1 and COX-2 enzymes. This pathway leads to the formation of an intermediate, PGH2, which is then modified to create prostaglandins and thromboxanes.
The other route is the lipoxygenase (LOX) pathway, which uses lipoxygenase enzymes to oxidize arachidonic acid, resulting in the creation of leukotrienes and lipoxins. Unlike the COX pathway which creates ring structures in its products, the LOX pathway produces linear eicosanoids. The enzymes present in a cell determine which eicosanoids are produced in response to a given stimulus.
Major Eicosanoid Classes and Their Contributions
Prostaglandins are a diverse class. In addition to their roles in inflammation, pain, and fever, they also play a part in protecting the stomach lining from acid and regulating blood flow to organs.
Thromboxanes are primarily associated with hemostasis, the process that stops bleeding. They promote the aggregation of platelets and constriction of blood vessels to form clots.
Leukotrienes are contributors to allergic and inflammatory reactions. They are known for causing contractions of the smooth muscles lining the airways, a feature of asthma attacks.
In contrast to the pro-inflammatory roles of other eicosanoids, lipoxins function to resolve inflammation. These molecules are anti-inflammatory, helping to halt the process once it is no longer needed. They work by inhibiting the recruitment of immune cells and promoting the clearance of cellular debris.
Eicosanoids: Balancing Health and Disease
The body’s proper functioning relies on a regulated balance in the production of different eicosanoids. Pro-inflammatory types are generated to fight infection or repair injury, while anti-inflammatory ones are produced to resolve the response. This equilibrium is important for maintaining tissue integrity and overall health.
Disruptions in this balance can lead to the development or worsening of diseases. Chronic inflammation, driven by excessive production of pro-inflammatory eicosanoids, is a feature of conditions like rheumatoid arthritis. An overproduction of leukotrienes can contribute to asthma, while an imbalance between clotting and anti-clotting eicosanoids can affect cardiovascular health.
Many common medications target the synthesis of eicosanoids. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, work by inhibiting the cyclooxygenase (COX) enzymes. By blocking these enzymes, the drugs reduce the production of prostaglandins, which in turn alleviates pain, fever, and inflammation.