Inflammation Dynamically Regulates Steroid Hormone Metabolism and Action Within Macrophages in Rheumatoid Arthritis

This study investigates the role of steroid metabolism in macrophages within rheumatoid arthritis (RA), revealing that inflammatory macrophages significantly increase the activation of glucocorticoids and androgens, which suppress inflammation. RNA-seq data from RA synovial macrophages showed changes in genes related to steroid metabolism, correlating with disease activity and pain. Key enzymes like 11β-HSD1, SRD5A1, and AKR1C3 were identified as crucial in this process, with 11β-HSD1 playing a novel role in androgen activation. The study highlights that increased glucocorticoid and androgen levels in macrophages and fibroblast-like synoviocytes help reduce inflammation. Additionally, the reduced presence of inactive steroid precursors in postmenopausal women may lead to higher disease incidence and severity.