Inverse temporal changes of lipoxin A4 and leukotrienes in children with Henoch–Schönlein purpura

The pathogenesis of Henoch–Schönlein purpura (HSP) is not clearly understood. It remains unclear how changes of lipoxin A4 (LXA4) that acts as a “braking signal” in inflammatory process occur in patients with HSP. In this study, we determined the temporal changes of blood and urinary LXA4, Leukotriene (LT)B4 and urinary LTE4 in 49 children with HSP. Inverse temporal changes between gradually increased blood and urinary LXA4 and gradually decreased blood and urinary LTB4 and urinary LTE4 were found in patients with HSP. Furthermore, both 15-S-hydroxyeicosatetraenoic acid and LXA4 inhibited the LTB4-induced chemotaxis of leukocytes and release of LTB4 from leukocytes obtained from the patients in the active phase of HSP. In 22 children with HSP nephritis, concordant with the gradually increased severity of mesangial proliferation and proteinuria, the glomerular expressions of 15-lipoxygenase and the levels of urinary LXA4 gradually decreased and the glomerular expressions of LTC4 synthase and the urinary LTE4 and LTB4 gradually increased. The levels of blood and urinary LXA4 in patients with HSP nephritis were lower than those in patients with purpura alone in early resolution of HSP. The levels of blood and urinary LTB4 and urinary LTE4 in the patients with HSP nephritis were higher than those in patients with purpura alone in early resolution of HSP. There was positive correlation between blood LTB4 and serum C-reactive protein in 49 children with HSP. These data suggest that LTs may play a proinflammatory and profibrotic role in the pathogenesis of HSP, and insufficiency of LXA4 may be responsible for the patients with HSP whose illness become more serious.