Background Macrophage migration inhibitory factor (MIF) is a key regulator of both atherosclerosis and systemic lupus erythematosus (SLE), yet the factors participating in its production remain unclear.

Objectives In this study, the relationship between type I interferon (IFN) and MIF levels in SLE patients were examined, and the effect as well as the mechanism of artesunate (ART), an anti-malarial agent extracted from Chinese herbs, on the regulation of MIF were explored.

Methods Serum and peripheral blood cells from SLE patients and healthy controls were collected, with MIF levels measured by ELISA and type I IFN inducible gene expressions detected by real-time PCR. Associations between two factors were assessed by Spearman correlation analysis. ART at different concentrations was added to human umbilical vein endothelial cells (HUVECs) cultures with or without prior IFNα-1bstimulation and to SLE peripheral blood mononuclear cells (PBMC) cultures, with dexamethasone or fludarabine, a selective inhibitor of signal transducer and activator of transcription (STAT) 1, applied as positive treatment controls. Protein levels of STATs and phosphorylated (p-) STATs in HUVECs were determined by western blotting.

Results Serum MIF levels were elevated in SLE patients and positively associated with disease activity (r =0.86, p <0.0001) and accumulated damage (r =0.34, p =0.048). Meanwhile, increased MIF levels were closely associated with IFN scores in SLE patients (r =0.74, p =0.0002). In vitro experiments showed that IFNα-1b had a direct impact on MIF production. ART could inhibit IFN inducible gene (LY6E and ISG15) expressions in HUVECs and PBMC cultures, and suppress IFNα-1b induced MIF production. Over-expression of p-STAT1, but not p-STAT3 or STAT5, was detected after IFNα-1b stimulation, which was completely reversed at the presence of ART.

Conclusions MIF could be regulated by type I IFN in SLE patients. ART counteracts the effect of IFNα to inhibit MIF production by blocking STAT1 phosphorylation, thus may have therapeutic potential for SLE-associated atherosclerosis.

Disclosure of Interest None declared