Anti-Tumor Necrosis Factor alpha Targets Protein Kinase B/c-Akt-Induced Resistance of Effector Cells to Suppression in Juvenile Idiopathic Arthritis

作者：Wehrens Ellen J; Vastert Sebastiaan J; Mijnheer Gerdien; Meerding Jenny; Klein Mark; Wulffraat Nico M; Prakken Berent J; van Wijk Femke^*

来源：Arthritis and Rheumatism, 2013, 65(12): 3279-3284.

DOI：10.1002/art.38132

ObjectiveTo determine whether therapeutic strategies that block interleukin-6 (IL-6) or tumor necrosis factor (TNF) can improve the responsiveness of Teff cells to suppression in patients with juvenile idiopathic arthritis (JIA).
MethodsSynovial fluid mononuclear cells (SFMCs) from the inflamed joints of patients with JIA were cultured in the presence of etanercept or anti-IL-6 in vitro, and protein kinase B (PKB)/c-Akt activation and responsiveness to suppression were measured. In addition, the in vivo effects of TNF blockade were investigated using peripheral blood mononuclear cells obtained from patients before and after the start of etanercept therapy.
ResultsIn vitro treatment of SFMCs with anti-IL-6 led to improved Treg cell-mediated suppression of cell proliferation in some but not all patients. Blocking TNF with etanercept, however, clearly enhanced suppression, especially that of CD8+ T cells. In the presence of etanercept, PKB/c-Akt activation of Teff cells was reduced, and cells became more susceptible to transforming growth factor -mediated suppression, indicating that anti-TNF directly targets resistant Teff cells.
ConclusionThis study is the first to show that anti-TNF targets the resistance of Teff cells to suppression, resulting in improved regulation of inflammatory effector cells.

• 出版日期2013-12