Expression and role of interleukin-9 in Vogt-Koyanagi-Harada disease

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disease that can lead to blindness. This study was designed to investigate whether interleukin (IL)-9 plays a role in the development of VKH disease. METHODS: IL-9, IL-17, and interferon (IFN)-γ levels, present in the supernatants of cultured peripheral blood mononuclear cells (PBMCs) and CD4+T cells, were assessed with enzyme-linked immunosorbent assay. IL-9 mRNA expression in PBMCs was measured with real-time quantitative PCR. The proliferation of PBMCs in response to different doses of recombinant human IL-9 (rIL-9) was measured using the Cell Counting Kit-8 assay. RESULTS: IL-9 mRNA levels in PBMCs were statistically significantly elevated in patients with active VKH disease compared to those in patients with inactive VKH disease (p<0.05) and normal controls (p<0.05). Statistically significantly higher expression of IL-9 was observed in the supernatants of stimulated PBMCs (p<0.01) and CD4+ T cells (p<0.01) from patients with active VKH disease compared to that in cells from patients with inactive VKH disease and normal controls. rIL-9 at a concentration of 100 ng/ml did not induce proliferation of PBMCs (p>0.05). After the PBMCs and CD4+ T cells were stimulated with rIL-9 (100 ng/ml), the secretion of IL-17 was increased statistically significantly (p<0.05), whereas the level of IFN-γ was not statistically significantly altered (p>0.05). CONCLUSIONS: These findings suggest that IL-9 is involved in the pathogenesis of VKH disease, and that IL-9 might also enhance the inflammatory response by increasing the secretion of IL-17, an established proinflammatory cytokine in VKH disease. Manipulation of IL-9 could represent a novel option for the treatment of VKH disease.