The critical role of IL-6 in the pathogenesis of Takayasu arteritis.

Abstract

OBJECTIVES: To investigate T cell subsets and immune cytokine profiles in untreated Takayasu arteritis (TAK) patients and the underlying immunopathological mechanism. METHODS: We enrolled 50 untreated TAK patients and 40 age-matched controls (20 healthy controls, 20 untreated SLE patients). Enzyme-linked immunosorbent assays (ELISAs) were used to define cytokine profiles in all patients, and flow cytometry was performed for 9 TAK patients and 12 healthy controls. Hematoxylin and eosin (Handamp;E) staining and immunohistochemistry (IHC) were performed in aortic tissues of 9 TAK and 9 atherosclerosis patients; clinical data were also collected. RESULTS: Circulating CD4(+) T cells were more frequent in TAK patients (p<0.05). Frequencies of Th1, Th2, and Th17 cells were higher, whereas Treg cells were reduced in TAK. Significantly higher levels of IL-6 and lower levels of IFN-γ, IL-4, and IL-17 were detected in TAK patients (p<0.05). By H & E staining, thickened vascular walls with proliferation of collagen fibre were observed in most patients. Inflammatory sites with infiltrating macrophages, lymphocytes, and neutrophils were located in adventitia. IHC revealed T cells (mainly CD4(+) T cells) in vascular lesions. Additionally, IL-6 was positive throughout the vascular wall in most specimens, whereas IFN-γ, IL-12, and IL-17 were detected in inflammatory sites of active patients. IL-6 levels were positively related to ESR, CRP, and Kerr scores (p<0.05). CONCLUSIONS: Significantly increased levels of IL-6 were detected in peripheral blood and aortic tissues of untreated patients. IL-6 might be a sensitive biomarker to assess disease activity and could be critical in the immunopathogenesis of TAK.