Further analyses revealed the presence of IL-38 protein in the supernatant of the transduced THP-1 cells, and this supernatant reduced LPS-induced secretion of IL-6, TNF-α, and IL-23, but not IL-1β, by the parental THP-1 line, IL-6, and IL-23 secretion by LPS-stimulated M1 macrophages of healthy donors and IL-1β-induced IL-6 production by synovial fibroblasts of rheumatoid arthritis patients, suggesting an extracellular effect of the cytokine (137). This evidence concerns the gene IL6 and rheumatoid arthritis.