Down-Regulation of IL-۱۷ by Hydroxychloroquine (HCQ) in Hematopoietic Stem Progenitor Cells of Lupus Patients

While systemic lupus erythematosus (SLE) is known to involve heightened pro-inflammatory cytokine production within immune cells, a knowledge gap exists regarding the specific cytokine profile of circulating hematopoietic stem progenitor cells (HSPCs) in SLE patients. This study aims to address this by investigating the expression of key inflammatory cytokines within this specific cell population and to elucidate whether hydroxychloroquine (HCQ) treatment can regulate inflammatory cytokines of HSPCs in these patients. This investigation employed an in vitro approach to analyze the anti-inflammatory cytokine (TGF-β) and the pro-inflammatory cytokines (IL-۶ and IL-۱۷) expression profile in HSPCs derived from leukapheresis of both SLE and healthy control subjects. Flow cytometry was employed to analyze cytokine expression. Following a ۷۲-hour incubation, we assessed the potential impact of ۵ µM and ۲۵ µM HCQ on the expression of IL-۶, IL-۱۷, and TGF-β by HSPCs. Circulating HSPCs from SLE patients exhibited significantly higher levels of inflammatory cytokines compared to healthy controls. Notably, HCQ treatment at concentrations of ۵ µM and ۲۵ µM significantly down-regulated IL-۱۷ expression in SLE-derived HSPCs compared to the untreated control group (p < ۰.۰۰۰۱). Interestingly, HCQ did not impact IL-۶ levels in SLE subjects. TGF-β levels remained unchanged following HCQ treatment in both groups. These observations suggest a potential role for HCQ in specifically reducing IL-۱۷ in SLE patients. This in vitro study provides evidence for heightened pro-inflammatory cytokine production within cultured HSPCs isolated from SLE patients. Furthermore, HCQ treatment demonstrates a potential capacity to inhibit this pro-inflammatory cytokine production in the SLE context.

Keywords:

Hematopoietic Stem Progenitor Cells (HSPC) , Hydroxychloroquine (HCQ) , systemic lupus erythematosus (SLE) , inflammatory cytokines