Introduction
Inflammation is the body’s normal response to disease and injury. It is elementary in the pathogenesis of various diseases. Inflammation is a beneficial event that leads to noxious stimuli removal and restoration of tissue structure and function. The acute phase of inflammation (which occurs immediately and lasts for a few days) is characterized by the rapid inflow of leukocytes (also called white blood cells, neutrophils, and monocytes). The outcome of acute inflammation is successful resolution and repair of tissue damage. A failure of resolution of acute inflammation can predispose to chronic inflammation (may last for a long time if acute inflammation fails to resolve), autoimmunity, and excessive tissue damage.
Prostaglandins (PGs) are lipids with hormone-like actions that the body makes mainly at sites of tissue damage. Their synthesis increases in inflamed tissue contributing to the fundamental signs of acute inflammation (redness, swelling, heat, and pain). The properties of individual PGs during the acute inflammatory response are proven, but their role in the resolution of inflammation is debatable.
Are Prostaglandins Required in the Body?
PGs are necessary for normal body circumstances and function. They have a great influence over natural body processes, including pain and inflammation. The normal inflammatory process is the body’s way of protection from further damage. However, sometimes the body can have excessive amounts of prostaglandins. As a result, it can lead to prolonged inflammation and intense pain. Hence, high PG levels can lead to chronic conditions and unpleasant symptoms.
What Is the Role of Prostaglandins in Inflammation?
PGs are lipid molecules derived from arachidonic acid (a fatty acid). There are several PGs and their receptors affecting every part of the body. Their effects depend on multiple factors, including the involved organ, the receptor, and the situation. PGs have a short duration of action. It is because they can only affect the nearby cells. Several different tissues throughout the body can make prostaglandins.
Prostaglandin E2 (PGE2 ), prostacyclin (PGI2), prostaglandin D2 (PGD2), and prostaglandin F2α (PGF2α) are the four PGs in the body. During an inflammatory response, the level of PG production changes. Initially, it is low in uninflamed tissues but increases before the infiltration of immune cells.
1. PGE2 and Inflammation: PGE2 is one of the most abundant PGs in the body and exhibits diverse biological actions. Under normal conditions, PGE2 is an essential regulator of inflammation, blood pressure, gastrointestinal (stomach and intestinal) integrity, kidney function, and fertility. Dysregulated PGE2 synthesis or degradation is linked to a wide range of pathologies. PGE2 is of particular interest as it is involved in all signs of inflammation.
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Redness and swelling occur after an increased blood flow to the inflamed tissue through blood vessel dilation and permeability.
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Pain results from its action on peripheral sensory nerve endings and sites within the spinal cord and the brain.
2. PGI2 and Inflammation: PGI2 regulates cardiovascular (heart) homeostasis (normal function). Endothelial cells (inner layer of blood vessels) and blood vessel smooth muscle cells are the sources of PGI2. PGI2 is a potent vasodilator, platelet aggregation inhibitor, and leukocyte adhesion (all these are involved in inflammation). These actions are mediated through specific receptors (expressed in the kidney, liver, lung, platelets, and heart).
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PGI2 is an important mediator of swelling and pain in acute inflammation. It is immediately produced after tissue injury or inflammation in high concentrations.
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Also, PGI2 is found in abundance in synovial fluid in knee joints during arthritis (knee inflammation).
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The PGI2 receptor is also expressed in the spinal cord and is involved in pain transmission. Hence, it is a part of the survival response to protect damaged tissue and prevent further damage.
3. PGD2 and Inflammation: PGD2 is synthesized in the brain and peripheral tissues. It functions both in inflammation and homeostasis. In the brain, PGD2 is involved in sleep regulation and other activities. In peripheral tissues, PGD2 is produced by mast cells (a type of immune cell) and other leukocytes. PGD2 is the predominant PG produced by activated mast cells (which are involved in acute allergic responses). Studies show that an allergen can trigger PGD2 production in sensitized individuals.
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The PGD2 receptor is expressed on the bronchi (bronchus is the air passage to the lungs) and mediates the production of inflammatory mediators that recruit inflammatory cells. As a result, it leads to airway inflammation and hyperreactivity in asthma. Hence, PGD2 is involved in acute allergic asthma.
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Also, PGD2 may play a role in atherosclerosis (plaque buildup in the artery). In the inflamed blood vessel, PGD2 prompts the inflammatory cells to increase the permeability of the blood vessels.
4. PGF2α and Inflammation: PGF2α is found in larger quantities in blood and urine in normal conditions and acute and chronic inflammation. PGF2α plays a pertinent role in ovulation, uterine smooth muscle contraction, and initiation of childbirth. Recent studies reveal that PGF2α also plays a role in renal function, brain injury, and pain. Also, PGF2α administration leads to acute inflammation.
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Cardiovascular risk factors such as diabetes, obesity, and smoking are associated with elevations in PGF2α.
The simplified and collective action of PGs at a local injury site is as follows.
After an injury, the affected tissue releases PGs signaling platelets in the blood to stick together to form a blood clot to stop the bleeding (platelet aggregation). Also, PGs narrow the affected blood vessels to decrease blood loss (vasoconstriction). Then the PGs trigger the inflammatory response, causing blood vessels to leak fluid into the tissues (swelling after vasodilation). It isolates any foreign body from further contact with the body. PGs involved with inflammation also attract leukocytes involved in the immune response. And, once healing completes, the affected tissue releases PGs to dissolve the blood clot and remove it.
What Are the Applied Aspects of Prostaglandins Related to Inflammation?
PGs and their analogs can treat glaucoma and elevated eye pressure (ocular hypertension). They are also used for labor induction, vasodilation, pulmonary (lung) hypertension, and localized scleroderma (an autoimmune connective tissue disorder). Since high levels of PGs can cause excessive pain and inflammation, doctors use medications to inhibit the effects of prostaglandins. The most commonly used medications that block the prostaglandins are nonsteroidal anti-inflammatory drugs (NSAIDs, also called painkillers).
Conclusion
Prostaglandins can be rightly called a double-edged sword. Sometimes, the body does not produce enough prostaglandins to heal an injury. Hence, synthetic prostaglandins are used in such a situation. Although they are necessary for healing and other functions, excess prostaglandins can cause chronic pain and inflammation and affect the quality of life. However, there is limited information on how they serve many roles. Hence, rigorous evidence regarding the same is required.
