Increased Interleukin-35 suppresses peripheral CD14+ monocytes function in patients with Kawasaki disease

Background Interleukin-35 (IL-35) is a newly identified IL-12 cytokine family member, which regulates the activity of immune cells in infectious diseases and autoimmune disorders. However, the regulatory function of IL-35 in Kawasaki disease is not well elucidated. Methods Thirty-three patients with Kawasaki disease and seventeen healthy controls were studied. Peripheral IL-35 concentration was measured by enzyme linked immunosorbent assay. CD14(+) monocytes were purified, and mRNA expression of IL-35 receptor (IL-12R beta 2 and gp130) was semi-quantified by real-time polymerase chain reaction. CD14(+) monocytes were stimulated with recombinant IL-35. The modulatory role of IL-35 treated CD14(+) monocytes to naive CD4(+) T cell activation was investigated by flow cytometry. The influence of IL-35 to cytotoxicity of CD14(+) monocytes was assessed by measuring target cell death, cytokine and granzyme secretion. Results Plasma IL-35 concentration was elevated in patients with Kawasaki disease. There was no significant differences of either IL-12R beta 2 or gp130 mRNA expression in CD14(+) monocytes between Kawasaki disease patients and controls. IL-35 suppressed CD14(+) monocytes induced naive CD4(+) T cell activation in Kawasaki disease, and this process required direct cell-to-cell contact. IL-35 also inhibited tumor necrosis factor-alpha and granzyme B secretion by CD14(+) monocytes from patients with Kawasaki disease, however, only granzyme B was responsible for the cytotoxicity of CD14(+) monocytes. Conclusions IL-35 played an important immunosuppressive role to CD14(+) monocytes function in Kawasaki disease.