Biochemical mediators involved in the inflammatory reaction. Protective activity of S 5682

Increased vascular permeability of inflammation is accounted for by the formation/release of mediators, such as lipids derived from arachidonate (eicosanoids: prostaglandins, thromboxane A2 or leukotrienes) or from ether phospholipids (PAF-acether). Acute inflammation can be controlled by inhibitors of mediator synthesis or by antagonists, as well as at the level of the reactivity of vascular endothelium or leukocytes. This modulation can be obtained with flavonoids, such as S 5682, a precise fraction of diosmin and hesperidin, which reduces the vascular permeability of the rabbit skin and increases the resistance of rat microvessels. After chronic treatment by the oral route with S 5682, the synthesis of PGE2, PGF2 and TxB2 decreased in inflammatory granuloma in the rat, induced by introducing subcutaneously polyurethane pellets. We carried out studies to see if S 5682 modifies the amounts of TxB2, of PGE2 and of PGI2 formed by perfused guinea-pig lungs injected with PAF-acether (1-100 ng). At 5-50 microM, S 5682 favoured the formation of PGE2 and of prostacyclin, and less that of thromboxane. At higher concentrations, the stimulation of the formation of eicosanoids was less marked, suggesting a biphasic effect. The biosynthetic profile of eicosanoids was affected at low concentrations the flavonoids with a complex and original pattern.