Elevated Expressions of 15-Lipoxygenase and Lipoxin A4 in Children with Acute Poststreptococcal Glomerulonephritis

Anti-inflammatory effects of the 15-lipoxygenase (15-LO) derivatives lipoxin A₄ (LXA₄) and 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) have been documented in many experimental models of acute inflammation. However, the expression levels of 15-LO and its products in human renal diseases remain unknown. This study investigated the expression levels of LXA₄, leukotriene B₄ (LTB₄), and 15-LO in leukocytes and glomeruli obtained from 22 children with acute poststreptococcal glomerulonephritis (APSGN), and determined the modulatory effects of both 15-S-HETE and LXA₄ on LTB₄ synthesis in leukocytes and LTB₄-evoked chemotaxis of polymorphonuclear leukocytes (PMNs) obtained from children during the first 3 days after onset of APSGN. Expression levels of both LXA₄ and 15-LO in leukocytes and glomeruli were up-regulated during the acute phase of disease, further peaking between days 10 and 14, and remained increased after 6 to 8 weeks of APSGN onset. In contrast, blood and urinary levels of LTB₄ as well as the number of glomerular PMNs peaked during the acute phase of disease and then decreased during the resolution phase. Administration of both 15-S-HETE and LXA₄ in vitro inhibited LTB₄-induced chemotaxis of PMNs and production of LTB₄ from leukocytes obtained from patients with APSGN. The current study provides further support for an anti-inflammatory role for 15-LO products in human nephritis through both antagonism and inhibition of leukotriene synthesis and its biological activity.