Increased biosynthesis of vasoactive prostanoids in Schönlein-Henoch purpura

Schönlein-Henoch purpura (SHP) is an acute immune-mediated vasculitis characterized by infiltration of polymorphonuclear leukocytes into the vessel wall causing damage to the vascular endothelium by the release of proteolytic enzymes. The local inflammatory and thrombotic process may be regulated by increased biosynthesis of vasoactive prostanoids. We investigated the biosynthesis of thromboxane A2 (TxA2), a potent vasoconstrictor and platelet agonist, prostacyclin (PGI2), a vasodilator and platelet antagonist, and prostaglandin E2, a mediator of inflammation, in 14 children with SHP by physicochemical analysis of index metabolites in plasma and urine. TxA2 and PGI2 biosynthesis in the systemic circulation was significantly elevated in the acute phase of the disease and correlated with the degree of clinical symptoms. Recurrent episodes of the disease were associated with phasic increases of plasma and urinary TxA2 and PGI2 metabolites. Renal TxA2 formation was highest in two patients presenting with the nephrotic syndrome and extracapillary glomerulonephritis. Prostaglandin E2 biosynthesis in the systemic circulation was increased in the acute phase of the disease. The enhanced TxA2 formation is consistent with phasic platelet activation in SHP. The increased PGI2 biosynthesis reflects endothelial cell damage and may be a response of vascular endothelium to modulate platelet-vessel wall and leukocyte-vessel wall interactions. Increased prostaglandin E2 formation, which probably derives from activated polymorphonuclear leukocytes and macrophages, is thought to be related to the inflammatory process in SHP.