Up regulation of the production of tumour necrosis factor α and interferon γ by T cells in ankylosing spondylitis during treatment with etanercept
Up regulation of the production of tumour necrosis factor α and interferon γ by T cells in ankylosing spondylitis during treatment with etanercept
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DOI：
10.1136/ard.62.6.561
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发表时间：
2003-06-01
影响因子：
27.4
通讯作者：
Sieper, J
中科院分区：
文献类型：
--
作者：
Zou, J;Rudwaleit, M;Sieper, J
背景资料：用重组可溶性肿瘤坏死因子α（TNF α）受体分子依那西普治疗活动性强直性脊柱炎（AS）已被证明具有高度的临床疗效。确切的作用机制，然而，是未知的。目的：为了评估在依那西普treatment.Patients和方法：外周血单个核细胞从10例患者与AS治疗25毫克依那西普和10例患者与AS治疗安慰剂治疗期间，每周两次皮下给药的细胞因子分泌能力的CD 4+和CD 8 + T细胞和巨噬细胞的变化。通过流式细胞术研究体外刺激后T细胞产生细胞因子的情况。12周的依那西普治疗诱导了干扰素γ数量的显著增加，（IFN γ）阳性（14.2%（9.6-19.5%））前v 24.4%（13.4-36.4%）和TNF α阳性CD 4 + T细胞（两种细胞因子p=0.008）和IFN γ阳性（37.5%（19.0-45.4%）之前v 52.9%）（33.2-60.0%）和TNF α阳性的CD 8 + T细胞（两种细胞因子的p=0.008），但在安慰剂组中没有。此外，依那西普治疗诱导IFN γ阳性CD 8 + T细胞的数量显著增加，（在12周时p=0.024）和在用聚集蛋白聚糖衍生肽体外刺激后TNF α阳性CD 8 + T细胞的非显著增加。外周TNF α的中和不诱导T细胞产生TNF α的能力的下调，而是上调，这可能是由于一种反调节机制。
Background: Treatment of active ankylosing spondylitis (AS) with the recombinant, soluble tumour necrosis factor a (TNFalpha) 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 gamma (IFNgamma) positive (14.2% (9.6-19.5%) before v 24.4% (13.4-36.4%) after) and TNFalpha positive CD4+ T cells (p=0.008 for both cytokines) and IFNgamma positive (37.5% (19.0-45.4%) before v 52.9% (33.2-60.0%) after) and TNFalpha 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 IFN gamma positive CD8+ T cells (p=0.024 at 12 weeks) and a non-significant increase of TNFalpha positive CD8+ T cells after in vitro stimulation with the aggrecan derived peptides.Conclusions: Neutralisation of peripheral TNFalpha does not induce a down regulation of the ability of T cells to produce TNFalpha but rather an up regulation, possibly due to a counterregulatory mechanism.