Methylprednisolone normalizes superoxide anion production by polymorphs from patients with ANCA-positive vasculitides

Daniela Macconi, Adrian Fabio Zanoli, Silvia Orisio, Lorena Longaretti, Luca Magrini, Stefano Rota, Antonella Radice, Cristiana Pozzi, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

It has been convincingly documented that reactive oxygen species released from activated neutrophils mediate glomerular damage in experimental glomerulonephritis. Recent findings that antineutrophil cytoplasmic autoantibodies (ANCA) induce neutrophils to degranulate and produce oxygen radicals in vitro led us to explore whether neutrophils from patients with ANCA-positive vasculitides and necrotizing glomerulonephritis generated an increased amount of superoxide anion (O2 -). Since glucocorticoids inhibit oxygen radicals generation in vitro we also evaluated the effect of intravenous pulses of methylprednisolone. Polymorphs were isolate from peripheral blood collected before (basal), 6 and 24 hours after the first infusion of methylprednisolone and 24 hours after the third one. O2 - release by cells was assessed after 30 minute incubation without specific stimuli. Basal O2 - release was significantly higher in patients than in controls (P>0.01). Intravenous infusion of high doses of methylprednisolone markedly reduced O2 - production with respect to the basal value, and the difference was statistically significant at various time interval considered after the steroid infusion. Besides reducing the excessive O2 - formation, methylprednisolone induced an increase in polymorph expression of the gene encoding for manganese superoxide dismutase (Mn-SOD) enzyme. We conclude that polymorphs taken from patients with ANCA-positive vasculitides and necrotizing glomerulonephritis generate higher amounts of O2 - than those from normal subjects. Methylprednisolone normalizes the abnormal generation of O2 -, likely through its ability to up-regulate the gene for Mn-SOD, a potent antioxidant enzyme.

Original languageEnglish
Pages (from-to)215-220
Number of pages6
JournalKidney International
Volume44
Issue number1
Publication statusPublished - Jul 1993

ASJC Scopus subject areas

  • Nephrology

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