title: The critical role of IL-6 in the pathogenesis of Takayasu arteritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Wanlong
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Zongfei
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Lingying
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Zhuojun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Rheumatology, Changhai Hospital affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Shengming
authors.initials: S
authors.lastname: Dai
authors.affiliation: Department of Rheumatology, Ren Ji Hospital affiliated to Jiaotong University, Shanghai, China.
authors.forename: Chengde
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China. zsh-rheum@hotmail.com.
authors.forename: Lindi
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013625:Takayasu Arteritis / Q000209:etiology* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6