Chemical Mediators of Inflammation: ARACHIDONIC ACID METABOLITES

1. What is arachidonic acid
Arachidonic acid is a polyunsaturated fatty acid present in the phospholipids of the cell membranes. Normally it is esterified to these phospholipids. This bound arachidonic acid is freed by the action of phospholipase A2 enzyme which is activated during inflammation as a result of increase in intracellular calcium levels.

2. What are the major arachidonic acid metabolites and how are they produced.
Prostaglandins and leukotrienes are the major metabolites of arachidonic acid which are synthesized by two pathways namely cyclooxygenase and lipoxygenase pathways respectively.
The synthesis of these metabolites are explained in the illustration below

3. What are the roles of arachidonic acid metabolites in inflammation
These metabolites can mediate possibly every step in inflammation. The roles of these metabolites are as below.
Vasodilation : PGD2, PGE2, PGF2α , prostacyclin, Lipoxin A4 & B4
Vasoconstriction: Thromboxane A2, Leukotriene C4, D4 & E4
Brondhodilation: PHD2, PGE2 and prostacyclin
Bronchoconstriction: PGF2α, Thromboxane A2, Leukotriene C4, D4 & E4
Promotes platelet aggregation: Thromboxane A2
Inhibits platelet aggregation: Prostacyclin
Chemoattractant: LeukotrieneB4
Inhibits chemotaxis :lipoxin A4 & B4
In addition, Prostaglandins also mediate Pain and fever which are the important systemic manifestation of inflammation
The above roles are explained in the illustration below

4. What are the therapeutic implications of understanding the roles of arachidonic acid metabolites in inflammation
Since , these mediators can mediate possibly every step of inflammation, Inhibition of the production of these mediators can SUPRESS INFLAMMATION.
Non steroidal inflammatory agents like aspirin, ibuprofen which are cyclooxygenase inhibitors, suppress prostaglandin synthesis and thereby reducing inflammation , pain and fever.
Zileuton a 5-lipoxygenase inhibitor inhibits production of leukotrienes( which causes bronchoconstriction) and thereby used in the treatment of bronchial asthma
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