Influence of anti-tumor necrosis factor (TNF) treatments on T cell cytokine production in patients with inflammatory joint diseases - comparison of etanercept and anti-TNF monoclonal antibodies. A double-blind, prospective, placebo-controlled study.

Abstract

Despite similar clinical effectiveness of tumor necrosis factor (TNF) inhibitors in the treatment of inflammatory joint diseases, they differ in effectiveness in other diseases and the exact mechanisms of their actions remain unclear. The aim of this study was to determine whether TNF inhibitors - etanercept and monoclonal antibodies affect intracellular cytokine production by T cell subsets. Anti-TNF-naive patients with inflammatory arthritis (rheumatoid arthritis or spondyloarthritis), characterized by high disease activity, were treated with TNF inhibitor - etanercept (14 patients) or monoclonal antibody (16 patients) for 12 weeks, while 11 patients received placebo. At baseline, 4, and 12 weeks after introducing anti-TNF treatment, intracellular production of TNF, interferon gamma (IFNγ), interleukin 17A (IL-17A), and IL-4 by T cell subsets was assessed using flow cytometry and analyzed by repeated measures two-way ANOVA. There were no differences in TNF, IFNγ, or IL-4-positive CD4, CD8, and CD3⁺CD4^-CD8^- (double negative, DN) cells between groups, neither while comparing effects of all TNF inhibitors jointly to placebo nor while analyzing effects in etanercept, monoclonal antibodies or placebo receiving groups. Similarly, there was no difference in IL-17A⁺CD4⁺ cells; however, a decrease in the percentage of IL-17A-positive DN T cells was observed in the etanercept-treated group (mean±SEM: 0.82±0.55, 0.41±0.16, 0.13±0.07) in comparison to placebo (0.23±0.10, 0.32±0.12, 0.49±0.15), (p=0.014), and an opposite; however, insignificant trend was observed in the monoclonal antibody-receiving group (0.41±0.13, 0.53±0.17, 0.82±0.3), (p=0.056 vs. etanercept). In summary, we ascertain that treatment with TNF inhibitors does not affect Th1, Th2, or Th17 responses. Etanercept and monoclonal antibodies differ in their effect on IL-17A+DN T cells.