Lipid mediators are chemical messengers that are released in response to tissue injury. When a harmful invader, such as bacteria, enters the body, some lipid mediators are released to help stimulate cells involved in the immune response while others help "turn off" an immune response when it is no longer needed. Current evidence suggests that lipid mediators, including prostaglandins (PGs), leukotrienes, and lipoxins, play an essential role in the different phases of inflammation.
Inflammation occurs when white blood cells flood to a site of injury in the body. The increase in these cells, which fight against disease-causing substances and/or heal the body, causes swelling in the body. Inflammation gradually subsides once the injurious stimulus has been destroyed or broken down by the body.
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Ulf von Euler of Sweden discovered prostaglandins (PGs) and isolated them from human semen in the 1930s. It was initially believed that prostaglandins were produced in the prostate gland, which is why they were named prostaglandins. It has since been determined that prostaglandins are produced in nearly every cell in the body.
Prostaglandins are similar to hormones because they serve as chemical messengers. However, prostaglandins do not move to other places in the body. Instead, they work inside the cells where they are produced.
Prostaglandins activate the inflammatory response and produce symptoms of pain and fever in the body. When tissues become damaged, white blood cells migrate to the site to minimize tissue destruction and prostaglandins are produced to help stimulate cells involved in this response.
Different prostaglandins have different functions. For instance, when a blood vessel is damaged, a type of prostaglandin called thromboxane is released. This prostaglandin stimulates cells in the blood, called platelets, to form blood clots. This action reduces bleeding in the body and prevents further destruction.
Another type of prostaglandin, called PG12, has the opposite effect on thromboxane. PG12 is produced to stop blood clots from forming on the walls of blood vessels.
Other prostaglandins help induce reproductive processes, such as labor. For instance, PGE2 causes uterine contractions, which induces labor.
Prostaglandins are involved in several other organs as well. For instance, in the gastrointestinal tract, they inhibit the production of stomach acid and increase secretion of protective mucus. They also increase blood flow in the kidneys, which are responsible for filtering waste from the blood.
Drugs have been developed to inhibit prostaglandins from acting. For instance, nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin®, Advil®), block an enzyme called cyclooxygenase (COX), which is involved in the production of prostaglandins. Blocking the COX enzyme prevents prostaglandins from being produced and subsequently relieves symptoms of pain and fever.
Swedish biochemist Bengt Samuelsson first discovered leukotrienes in 1979. These mediators were first discovered in white blood cells derived from bone marrow (leukocytes).
Leukotrienes are inflammatory molecules that exhibit a wide range of biological activities, most of which involve sending signals or messages to other cells in the body.
There are two main types of leukotrienes: leukotriene B4 and cysteinyl leukotrienes. Leukotriene B4 is involved in inflammatory conditions that are dependent on white blood cells called neutrophils. When these leukotrienes are released into the blood, they signal neutrophils to move towards the site of injury in the body. Leukotriene B4 has also been associated with long-term conditions, such as cystic fibrosis, inflammatory bowel disease (IBD), and psoriasis.
Inflammatory cells called eosinophils and mast cells produce cysteinyl leukotrienes. When cysteinyl leukotrienes are produced, they signal more eosinophils and/or mast cells to move towards the site of injury in the body. These leukotrienes have also been associated with asthma and allergies.
Cysteinyl leukotrienes are one of severalsubstances that are released by mast cells during an asthma attack. These leukotrienes signal more mast cells to migrate toward the area causing the airway muscles to contract and mucus secretion to increase. As a result, the airways narrow and symptoms of asthma, including difficulty breathing and wheezing, occur. Long-term cases of asthma appear to be caused by inflammatory cells called eosinophils, which also release cysteinyl leukotrienes. Therefore, leukotrienes are capable of triggering both short-term asthma attacks and long-term asthma symptoms.
Drugs have been developed to prevent leukotrienes from having negative effects on the body. For instance, both leukotriene synthesis inhibitors, such as zafirlukast (Accolate®), and cysteinyl-leukotriene receptor antagonists, such as montelukast (Singulair®) and zileuton (Zyflo®), have been shown to prevent asthma attacks in asthmatic patients. However, these drugs are not effective treatments once the asthma attack has started.
Leukotriene synthesis inhibitors prevent mast cells or eosinophils from releasing leukotrienes. Cysteinyl leukotriene receptor antagonists block specific leukotriene receptors on bronchial tissues in the airway, which subsequently prevents the airway constriction, mucus secretion, and inflammation. Cysteinyl leukotriene receptor antagonists also reduce the influx of eosinophils, which reduces inflammatory damage in the airways.
Lipoxins (LXs) are anti-inflammatory mediators. Unlike prostaglandins and leukotrienes, the lipoxins signal the resolution of inflammation.
Once the injurious stimulus, such as bacteria, has been removed from the body, destroyed, or broken, lipoxins are released to stop the inflammatory response. When lipoxins are released, the white blood cells are no longer signaled to move toward the site of injury. As a result, inflammation in the body decreases.