Effect of Interleukin-34 on Secretion of Angiogenesis Cytokines by Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis

Background: Interleukin (IL)-34 is a new pro-inflammatory cytokine. Previous studies showed that IL-34 plays a key role in inflammation and osteoporosis in rheumatoid arthritis (RA). However, whether IL-34 participates in angiogenesis in RA remains unknown. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1 alpha) play critical roles in the angiogenesis of RA. Methods: 22 patients with RA, 18 patients with ankylosing spondylitis (AS), and 8 healthy subjects were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and purified from peripheral blood by density gradient centrifugation. PBMCs were stimulated using anti-CD3/CD28 antibody and different concentrations of recombinant human (rh) IL-34 (0, 10, 20, 50, 100 ng/mL). Cell-free supernatants were collected after 72 h incubation, and VEGF and HIF-1 alpha levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: IL-34 promotes the secretion of VEGF and HIF-1 alpha by PBMCs in RA patients in a dose-dependent manner. In contrast, IL-34 has no effect on VEGF and HIF-1 alpha secretion by PBMCs in AS and healthy controls. Conclusion: IL-34 may indirectly contribute to angiogenesis by promoting the production of VEGF and HIF-1 alpha and participate in the pathogenesis of RA.