RT Journal Article
SR Electronic
T1 Up regulation of the production of tumour necrosis factor α and interferon γ by T cells in ankylosing spondylitis during treatment with etanercept
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 561
OP 564
DO 10.1136/ard.62.6.561
VO 62
IS 6
A1 J Zou
A1 M Rudwaleit
A1 J Brandt
A1 A Thiel
A1 J Braun
A1 J Sieper
YR 2003
UL http://ard.bmj.com/content/62/6/561.abstract
AB Background: Treatment of active ankylosing spondylitis (AS) with the recombinant, soluble tumour necrosis factor α (TNFα) receptor molecule etanercept has been shown to be clinically highly effective. The precise mechanism of action, however, is not known. Objective: To assess the change in the cytokine secreting ability of CD4+ and CD8+ T cells and macrophages during etanercept treatment. Patients and methods: Peripheral blood mononuclear cells from 10 patients with AS treated with 25 mg etanercept and 10 patients with AS treated with placebo were investigated during treatment given twice weekly subcutaneously. Production of cytokines by T cells was investigated after in vitro stimulation by flow cytometry. Results: Twelve weeks of etanercept treatment induced a significant increase in the number of interferon γ (IFNγ) positive (14.2% (9.6–19.5%) before v 24.4% (13.4–36.4%) after) and TNFα positive CD4+ T cells (p=0.008 for both cytokines) and IFNγ positive (37.5% (19.0–45.4%) before v 52.9% (33.2–60.0%) after) and TNFα positive CD8+ T cells (p=0.008 for both cytokines) upon phorbol myristate acetate/ionomycin stimulation, but not in the placebo group. Furthermore, etanercept treatment induced a significant increase in the number of IFNγ positive CD8+ T cells (p=0.024 at 12 weeks) and a non-significant increase of TNFα positive CD8+ T cells after in vitro stimulation with the aggrecan derived peptides. Conclusions: Neutralisation of peripheral TNFα does not induce a down regulation of the ability of T cells to produce TNFα but rather an up regulation, possibly due to a counterregulatory mechanism.