The University of Manchester, Division of Infection, Immunity & Respiratory Medicine, Manchester Academic Health Science Centre, The Medicines Evaluation Unit, Manchester University NHS Foundation Trust (South), Manchester, United Kingdom.
The University of Manchester, Division of Infection, Immunity & Respiratory Medicine, Manchester Academic Health Science Centre, The Medicines Evaluation Unit, Manchester University NHS Foundation Trust (South), Manchester, United Kingdom.
Cytokine. 2019 Jan;113:68-73. doi: 10.1016/j.cyto.2018.06.007. Epub 2018 Jun 19.
Lymphocytes play a key role in asthma pathophysiology, secreting various cytokines involved in chronic inflammation. CHF6001 is a highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor designed for inhaled administration and has been shown to reduce the late asthmatic response. However, the effect of PDE4 inhibition on the different cytokines produced by lung lymphocytes from asthma patients has not been examined.
This study investigated the anti-inflammatory effects of CHF6001 and the corticosteroid, 17-BMP, on T-cell receptor (TCR) stimulated Th1, Th2 and Th17 cytokine release from bronchoalveolar lavage (BAL) cells from mild (n = 12) and moderate asthma (n = 12) patients.
CHF6001 inhibited IFNγ, IL-2 and IL-17, but not IL-13, secretion from both mild and moderate asthma patient BAL cells; there was a greater effect on IFNγ and IL-2 than IL-17. The corticosteroid inhibited all four cytokines from both patient groups, but was less effective in cells from more severe patients. CHF6001 had a greater inhibitory effect on IFNγ and IL-2 than 17-BMP.
The PDE4 inhibitor CHF6001 had a greater effect on Th1 cytokines from TCR-stimulated BAL cells than corticosteroid. This pharmacological effect suggests the therapeutic potential for PDE4 inhibitors to be used in the subset of more severe asthma patients with increased airway levels of IFNγ.
淋巴细胞在哮喘病理生理学中发挥关键作用，分泌各种参与慢性炎症的细胞因子。CHF6001 是一种高效且选择性的磷酸二酯酶 4（PDE4）抑制剂，专为吸入给药而设计，已被证明可减少晚期哮喘反应。然而，PDE4 抑制对哮喘患者肺淋巴细胞产生的不同细胞因子的影响尚未被研究。
本研究调查了 CHF6001 和皮质类固醇 17-BMP 对 T 细胞受体（TCR）刺激的轻度（n=12）和中度哮喘（n=12）患者支气管肺泡灌洗液（BAL）细胞中 Th1、Th2 和 Th17 细胞因子释放的抗炎作用。
CHF6001 抑制 IFNγ、IL-2 和 IL-17，但不抑制 IL-13，从轻度和中度哮喘患者的 BAL 细胞中释放；对 IFNγ 和 IL-2 的抑制作用大于 IL-17。皮质类固醇抑制了来自两个患者组的所有四种细胞因子，但对更严重患者的细胞效果较差。CHF6001 对 IFNγ 和 IL-2 的抑制作用大于 17-BMP。
PDE4 抑制剂 CHF6001 对 TCR 刺激的 BAL 细胞中的 Th1 细胞因子的抑制作用大于皮质类固醇。这种药理作用表明 PDE4 抑制剂在 IFNγ 气道水平升高的更严重哮喘患者亚组中具有治疗潜力。
