Background An important contributor to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) is the impaired clearance of apoptotic cells (efferocytosis) and increasing evidence implicates microbiota dysbiosis as another important player. The disease-modifying antirheumatic drug hydroxychloroquine (HCQ) is frequently prescribed for the treatment of SLE. Here, we evaluate changes in efferocytosis and the gut microbiome in mice with pristane-induced lupus (PIL) before and after HCQ administration.
Methods PIL mice were studied with or without HCQ and/or resveratrol (RESV). Efferocytosis was determined in RAW 264.7 cells and peritoneal macrophages from mouse ascites fluid. The gut microbiome was analyzed using Illumina sequencing targeting the 16S ribosomal DNA gene (rDNA) amplicon sequencing.
Results Both HCQ and RESV enhanced efferocytosis. HCQ also significantly suppressed ascites production of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). The Firmicutes/Bacteriodetes (F/B) ratio was significantly decreased in PIL mice compared with untreated controls (p<0.05). The F/B ratio in PIL mice was increased by HCQ alone and significantly increased by HCQ combined with RESV. Alpha- and beta-diversity differed between mice administered RESV and those that were not. Viable counts of lactic acid bacteria Lactobacillaceae, Lactobacillus and Lactobacillales were increased by RESV plus HCQ treatment.
Conclusions In this study, HCQ and RESV enhanced efferocytosis in both RAW 264.7 cells and peritoneal macrophages of PIL mice and suppressed IL-6 and TNF-α production in ascites fluid. The pristane-induced reduction in the F/B ratio was restored by HCQ treatment. SLE treatment should consider the role of the gut microbiome.