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首页> 外文期刊>Veterinary Medicine and Science >Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12‐myristate 13‐acetate
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Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12‐myristate 13‐acetate

机译：免疫抑制剂对脂多糖或离子霉素和佛波醇12-肉豆蔻酸酯13-乙酸酯联合刺激的犬全血中细胞因子产生的影响

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A pharmacodynamic assay has been previously developed to monitor ciclosporin treatment in dogs by assessing inhibition of cytokine transcription after whole blood stimulation with 12‐myristate 13‐1 acetate and ionomycin (PMA/I). In this study, whole blood stimulation with either PMA/I or lipopolysaccharide (LPS) was used to assess the effect of multiple drugs (azathioprine, ciclosporin, mycophenolate, leflunomide and prednisone) after a 7‐day treatment course on production of cytokines measured with a multiplex assay in healthy dogs ( n ?=?4 for each treatment). Interleukin‐10 (IL‐10), interferon gamma (IFN γ ) and tumour necrosis factor alpha (TNF α ) were significantly activated by PMA/I stimulation and IL‐6, IL‐10 and TNF α by LPS stimulation, in the absence of immunosuppressive drugs. After ciclosporin treatment, IL‐10, IFN γ and TNF α production was significantly reduced after stimulation with PMA/I compared to pre‐treatment. After prednisone treatment, TNF α production was significantly reduced after stimulation with PMA/I or LPS compared to pre‐treatment. No significant change was observed after treatment with azathioprine, leflunomide or mycophenolate. This methodology may be useful to monitor dogs not only treated with ciclosporin, but also with prednisone or a combination of both. Further studies are needed to assess the use of this assay in a clinical setting.
机译：以前已经开发出一种药效学分析方法，通过评估用12-肉豆蔻酸13-1醋酸盐和离子霉素（PMA / I）刺激全血后对细胞因子转录的抑制，来监测犬环孢素的治疗。在这项研究中，使用PMA / I或脂多糖（LPS）进行全血刺激来评估多种药物（硫唑嘌呤，环孢素，霉酚酸酯，来氟米特和泼尼松）在经过7天的治疗过程后对细胞因子产生的影响。在健康犬中进行多重测定（每种治疗的n≤4）。在不存在PMA / I刺激的情况下，白介素10（IL-10），干扰素γ（IFNγ）和肿瘤坏死因子α（TNFα）被激活，而在LPS刺激下IL-6，IL-10和TNFα被LMA显着激活。免疫抑制药物。环孢素治疗后，与预处理相比，PMA / I刺激后IL-10，IFNγ和TNFα的产生显着降低。泼尼松治疗后，与预处理相比，PMA / I或LPS刺激后，TNFα的产生显着减少。用硫唑嘌呤，来氟米特或霉酚酸酯处理后未观察到明显变化。这种方法不仅可用于监测用环孢菌素治疗的狗，而且还可以监测泼尼松或两者的组合治疗的狗。需要进一步的研究来评估这种测定法在临床上的使用。

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