Increased Lipid Peroxidation May Be Linked to Ferritin Levels Elevation in Adult-Onset Still’s Disease

Abstract

Lipid peroxidation (LPO) and hyper-ferritinemia are involved in inflammatory responses. Although hyper-ferritinemia is a characteristic of AOSD, its link to LPO remains unclear. We investigated the association between LPO and ferritin expression, and evaluated the relationship between LPO-related metabolites and inflammatory parameters. Mean fluorescence intensity (MFI) of LPO (C11-Biodipy581/591)-expressing PBMCs/monocytes in AOSD patients and healthy control (HC) subjects was determined by flow-cytometry analysis. Expression of ferritin and cytokines on PBMCs/macrophages was examined by immunoblotting. Plasma levels of LPO-related metabolites and cytokines were determined by ELISA and the MULTIPLEX platform, respectively. LPO MFI on PBMCs/monocytes were significantly higher in patients (median 4456 and 9091, respectively) compared with HC (1900, p < 0.05, and 4551, p < 0.01, respectively). Patients had higher ferritin expression on PBMCs (mean fold, 1.02) than HC (0.55, p < 0.05). Their ferritin expression levels on PBMCs stimulated with LPO inducers erastin or RSL3 (2.47 or 1.61, respectively) were higher than HC (0.84, p < 0.05, or 0.74, p < 0.01). Ferritin expression on erastin-treated/IL-1β-treated macrophages from patients were higher than those from HC (p < 0.001). The elevated levels of LPO-related metabolites, including malondialdehyde and 4-hydroxyalkenals, were positively correlated with disease activity scores, suggesting LPO involvement in AOSD pathogenesis. Increased ferritin expression on PBMCs/macrophages stimulated with LPO inducers indicates a link between LPO and elevated ferritin.