Cytokines and regulatory T cells in ankylosing spondylitis

Aims To investigate the correlations among cytokines and regulatory T cells (T- regs) in ankylos-ing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-alpha (TNF-alpha) treatment.Methods We included 72 AS patients with detailed medical records, disease activity score (Bath An-kylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL) -2, IL -4, IL -10, TNF-alpha, interferon (IF-N)-gamma, transforming growth factor (TGF)-beta, ESR, and CRP). Their peripheral blood mononu-clear cells (PBMCs) were marked with anti- CD4, anti- CD25, and anti- FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T- regs. Their correlations were calcu-lated and the changes after anti- TNF-alpha therapy were compared.Results The frequency of T- regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-alpha and CRP (p = 0.041). The frequency of T- regs in PBMCs positively cor-related to serum levels of TNF-alpha, IL -10, and TGF-beta, while IL -2, IL -4, and IFN-gamma showed oppo-site results. After anti- TNF-alpha treatment, there were significantly lower serum levels of TNF-alpha, IL-10, TGF-beta, and frequency of T- regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively).Conclusion In AS patients, proinflammatory cytokine may give positive feedback to induce more T- reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti- TNF-alpha therapy. However, the detailed interactions among T- regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay.