explain in detail role of arachidonic acid derived mediators in various stages of acute inflammations

 

Arachidonic acid is a polyunsaturated fatty acid found in the cell membranes of various cells, including inflammatory cells like leukocytes and platelets. It plays a crucial role in the inflammatory response through the synthesis of different lipid mediators called eicosanoids. These eicosanoids are categorized into three major groups: prostaglandins, leukotrienes, and thromboxanes. In various stages of acute inflammation, arachidonic acid-derived mediators act as important signaling molecules that regulate vascular permeability, leukocyte recruitment, and inflammatory cell activation. Let's explore the role of these mediators in different stages of acute inflammation:

**1. Vasoconstriction:**

   - During the initial stage of inflammation, arterioles may undergo transient vasoconstriction, which serves as a protective mechanism to limit blood flow to the affected area and prevent the spread of toxins or pathogens.

**2. Vasodilation:**

   - Prostaglandins, especially PGE2 and PGD2, play a significant role in promoting vasodilation during inflammation. They act on vascular smooth muscle cells, causing relaxation and increasing blood flow to the site of injury or infection. This vasodilation results in the characteristic redness and heat observed at the inflamed area.

**3. Increased Vascular Permeability:**

   - Prostaglandins (PGE2 and PGD2) and leukotrienes (LTC4, LTD4, LTE4) induce increased vascular permeability. They act on endothelial cells lining blood vessels, leading to the formation of gaps between cells, allowing plasma proteins and immune cells to enter the affected tissue. This increased permeability results in edema (swelling) at the site of inflammation.

**4. Leukocyte Recruitment:**

   - Leukotrienes (LTC4, LTD4, LTE4) are potent chemoattractants for neutrophils, eosinophils, and other inflammatory cells. They help recruit these cells from the blood to the site of inflammation, facilitating the immune response and aiding in the clearance of pathogens.

**5. Activation of Inflammatory Cells:**

   - Thromboxane A2 (TXA2), synthesized from arachidonic acid in platelets, promotes platelet activation and aggregation. This helps in the formation of a hemostatic plug at the site of tissue injury.

   - Leukotrienes (LTC4, LTD4, LTE4) also contribute to the activation of leukocytes, enhancing their ability to release inflammatory cytokines and free radicals.

**6. Pain and Fever:**

   - Prostaglandins (PGE2) are involved in the generation of pain and fever during inflammation. They sensitize nociceptors (pain receptors) and stimulate the hypothalamus, resulting in an elevation of body temperature.

**7. Resolution of Inflammation:**

   - Lipoxins, another class of arachidonic acid-derived mediators, are produced during the later stages of inflammation. They play a crucial role in resolving inflammation by inhibiting leukocyte recruitment and promoting the clearance of apoptotic neutrophils.

Overall, arachidonic acid-derived mediators play diverse and crucial roles in various stages of acute inflammation, contributing to the regulation of vascular responses, recruitment and activation of inflammatory cells, and the resolution of inflammation. The balanced production and regulation of these mediators are essential for an effective inflammatory response, which aids in tissue repair and host defense against pathogens. However, dysregulation of these mediators can lead to chronic inflammation and various inflammatory disorders.

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MCQs on Arachidonic Acid-Derived Mediators in Inflammation

Q1. Arachidonic acid is a:

Q2. Which of the following are NOT arachidonic acid-derived mediators?

Q3. Which arachidonic acid-derived mediator is involved in vasodilation during inflammation?

Q4. Which arachidonic acid-derived mediator induces increased vascular permeability during inflammation?

Q5. Which arachidonic acid-derived mediator acts as a chemoattractant for neutrophils and eosinophils?

Q6. What role do thromboxanes play in inflammation?

Q7. Which arachidonic acid-derived mediator is involved in the generation of pain and fever during inflammation?

Q8. What is the role of lipoxins in inflammation?

Q9. Which arachidonic acid-derived mediator is involved in platelet activation and aggregation?

Q10. Dysregulation of arachidonic acid-derived mediators can lead to:

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