Arachidonic acid inflammatory cascade (AA cascade)

The arachidonic acid inflammatory cascade is a fundamental biochemical pathway that generates eicosanoids, a class of potent lipid signaling molecules including prostaglandins, thromboxanes, and leukotrienes [1, 6]. The cascade is initiated when phospholipase A2 (PLA2) releases arachidonic acid from cell membrane phospholipids in response to inflammatory stimuli [1, 12]. This free arachidonic acid is then processed by three main enzymatic systems: cyclooxygenases (COX-1 and COX-2), lipoxygenases (LOX), and cytochrome P450 (CYP) enzymes [1, 14]. These mediators regulate a wide array of physiological and pathological processes, such as inflammation, pain, fever, blood pressure, and platelet aggregation [6, 11]. Pharmacological modulation of this cascade is widely employed to treat inflammatory conditions, pain, and respiratory diseases [2, 4]. Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen target the COX pathway, while glucocorticoids provide broader suppression by inhibiting PLA2 and reducing enzyme expression [7, 12]. Specialized drugs like zileuton and montelukast target the LOX pathway to treat asthma [7]. Despite their efficacy, these drugs can cause significant side effects, including gastrointestinal ulcers and cardiovascular complications, often resulting from the disruption of the delicate balance between pro- and anti-inflammatory mediators within the cascade [4, 12].

Other names

Arachidonic acid pathwayEicosanoid synthesis pathwayAA metabolismProstaglandin synthesis pathway

Inhibition of enzymes within the cascade, including Phospholipase A2, Cyclooxygenase-1, Cyclooxygenase-2, and 5-Lipoxygenase, or antagonism of downstream eicosanoid receptors.