Actual Role of Prostaglandins in Inflammation

The prostaglandins (PGs) are a family of naturally occurring cyclopentane-containing carboxylic acids of varying degrees of unsaturation. They are produced from arachidonic acid, which is released from tissue phospholipids by the enzyme phospholipase A2. The enzyme cyclooxygenase is responsible for the conversion of free arachidonic acid into unstable cyclic peroxides (PGG2 and PGH2). These compounds are known as PG endoperoxides and are further transformed by specific enzymes into the different PGs, notably the thromboxanes and PGI2 (epoprostenol). PGs are not prestored in tissues, but are formed when activation of phospholipase or other lipases takes place in a tissue. This activation can result from various factors such as physiological stimuli (e.g. exercise, pregnancy, age), pharmacological stimuli [e.g. angiotensin, bradykinin, noradrenaline (norepinephrine)] or pathological stimuli (tissue injury or disease). PGs exhibit a number of biological effects, primarily upon those cells immediately surrounding the site of their synthesis, partly because they are rapidly inactivated. Prostanoids have been shown to have a wide range of effects on many physiological systems and a role for PGs in tissue inflammation and injury has been proposed. Over the years, evidence of the powerful pro-inflammatory action of PGs has accumulated, nevertheless, recent findings on anti-inflammatory effects of PGs, as well as on mechanisms of action of NSAIDs, other than inhibition of PG biosynthesis suggest a modulatory role for PGs in the inflammatory process