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

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.

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-12Rβ2 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 naïve 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.

Plasma IL-35 concentration was elevated in patients with Kawasaki disease. There was no significant differences of either IL-12Rβ2 or gp130 mRNA expression in CD14⁺ monocytes between Kawasaki disease patients and controls. IL-35 suppressed CD14⁺ monocytes induced naïve CD4⁺ T cell activation in Kawasaki disease, and this process required direct cell-to-cell contact. IL-35 also inhibited tumor necrosis factor-α and granzyme B secretion by CD14⁺ monocytes from patients with Kawasaki disease, however, only granzyme B was responsible for the cytotoxicity of CD14⁺ monocytes.

IL-35 played an important immunosuppressive role to CD14⁺ monocytes function in Kawasaki disease.