86. Neuroendocrine mediators regulate production of B cell activating factor of the tumor necrosis factor family (BAFF) in human synovial fibroblasts

Abstract

BAFF is a cytokine important for the stimulation and survival of autoreactive B cells and therefore might play a role in several autoimmune diseases. In psoriasis arthritis (PsA), we found that BAFF correlates with disease activity and testosterone, but only in male patients, suggesting a role for sex hormones in the regulation of BAFF. Therefore, we wanted to determine if BAFF in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts (SF) is regulated by neuroendocrine mediators. SF isolated from RA ( n = 10) and OA ( n = 10) patients were cultured in the presence or absence of Interferon- γ (IFN γ ), IL-1, lipopolysaccharide (LPS), tumor necrosis factor (TNF) or cortisol at different concentrations for 48 and 72 h. IFN- γ was used in subsequant experiments, because it was the best inductor of BAFF in RA and OA SFs. IFN- γ -induced BAFF production was decreased by dihydrotestosterone in a concentration-dependent manner at 24 h, however the effect was reversed after 72 h of culture. The effect was specifically inhibited by nilutamid, a testosterone receptor antagonist. Furthermore, α -adrenergic mechanisms decreased and β -adrenergic mechanisms increased BAFF in OA and RA SFs. In general the effects were more pronounced in RA as compared to OA SFs. Taken together, BAFF production in synovial fibroblasts is modulated by testosterone and adrenergic stimuli. Therefore, the influence of neuroendocrine mediators in the context of arthritis might be in part mediated by regulating BAFF.