BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells. OBJECTIVE: To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease. METHODS: Blood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4(+) T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti-IFN-gamma were determined by ELISA. RESULTS: The patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4(+) T cells. Recombinant IL-23 significantly enhanced IL-17 production, whereas rIL-12 and IFN-gamma inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-gamma production. CONCLUSION: The results suggest that IL-23-stimulated production of IL-17 by CD4(+) T cells may be responsible for the development of uveitis seen in patients with VKH disease. CLINICAL IMPLICATIONS: This study provides a new insight into the mechanism involved in the development of VKH disease.
BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells. OBJECTIVE: To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease. METHODS: Blood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4(+) T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti-IFN-gamma were determined by ELISA. RESULTS: The patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4(+) T cells. Recombinant IL-23 significantly enhanced IL-17 production, whereas rIL-12 and IFN-gamma inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-gamma production. CONCLUSION: The results suggest that IL-23-stimulated production of IL-17 by CD4(+) T cells may be responsible for the development of uveitis seen in patients with VKH disease. CLINICAL IMPLICATIONS: This study provides a new insight into the mechanism involved in the development of VKH disease.