Abstract
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.
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Figure 1.
A significant increase in the production of IFNγ and of TNFα by CD4+ T cells upon PMA/ionomycin stimulation was observed after 12 weeks of etanercept treatment in the etanercept group. *p=0.008, compared with before treatment, but no change in the cytokine production was detected after six weeks of etanercept treatment in the placebo group. The medians and ranges of non-specific cytokine production are indicated in the figure.
Figure 2.
A significant increase in the production of IFNγ and of TNFα by CD8+ T cells upon PMA/ionomycin stimulation is seen during etanercept treatment. No change in the cytokine production was detected after six weeks of treatment in the placebo group, but a significant increase in the production of IFNγ and of TNFα by CD8+ T cells upon PMA/ionomycin stimulation was seen after the patients were switched to etanercept treatment. The median and range of non-specific cytokine production are indicated in the figure. *p<0.05 compared with before treatment; #p=0.008 compared with before treatment.