PT  - JOURNAL ARTICLE
AU  - J Zou
AU  - M Rudwaleit
AU  - J Brandt
AU  - A Thiel
AU  - J Braun
AU  - J Sieper
TI  - Up regulation of the production of tumour necrosis factor α and interferon γ by T cells in ankylosing spondylitis during treatment with etanercept
AID  - 10.1136/ard.62.6.561
DP  - 2003 Jun 01
TA  - Annals of the Rheumatic Diseases
PG  - 561--564
VI  - 62
IP  - 6
4099  - http://ard.bmj.com/content/62/6/561.short
4100  - http://ard.bmj.com/content/62/6/561.full
SO  - Ann Rheum Dis2003 Jun 01; 62
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.