Grundy Seamus, Plumb Jonathan, Kaur Manminder, Ray David, Singh Dave
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust Southmoor Road, Manchester, M23 9LT, UK.
School of Medicine and Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Respir Res. 2016 Jan 25;17:9. doi: 10.1186/s12931-016-0325-8.
CD8 lymphocytes play an important role in the pathogenesis of COPD. Corticosteroids and phosphodiesterase 4 (PDE4) inhibitors are anti-inflammatory drugs used for COPD treatment. Little is known of the combined effect of these drugs on COPD CD8 cells. We studied the effect of corticosteroid combined with PDE4 inhibitors on cytokine release form circulating and pulmonary CD8 cells, and on glucocorticoid (GR) nuclear translocation.
The effect of dexamethasone alone and in combination with the PDE4 inhibitors roflumilast and GSK256066 on cytokine release from circulating and pulmonary CD8 cells was measured. The effect of the compounds on nuclear translocation of GR and cyclic AMP-responsive element-binding protein (CREB) was studied using immunofluorescence.
Dexamethasone inhibited cytokine release from COPD CD8 cells in a concentration dependent manner. PDE4 inhibitors enhanced this anti-inflammatory effect in an additive manner. PDE4 inhibitors did not increase corticosteroid induced GR nuclear translocation. PDE4 inhibitors, but not corticosteroid, increased phospho-CREB nuclear translocation.
The combination of corticosteroids and PDE4 inhibitors results in an additive anti-inflammatory effect in COPD CD8 cells. This enhanced anti-inflammatory effect could translate to important clinical benefits for patients with COPD.
CD8淋巴细胞在慢性阻塞性肺疾病（COPD）的发病机制中起重要作用。皮质类固醇和磷酸二酯酶4（PDE4）抑制剂是用于治疗COPD的抗炎药物。关于这些药物对COPD CD8细胞的联合作用知之甚少。我们研究了皮质类固醇与PDE4抑制剂联合使用对循环和肺CD8细胞细胞因子释放以及糖皮质激素（GR）核转位的影响。
测定地塞米松单独使用以及与PDE4抑制剂罗氟司特和GSK256066联合使用对循环和肺CD8细胞细胞因子释放的影响。使用免疫荧光研究这些化合物对GR和环磷酸腺苷反应元件结合蛋白（CREB）核转位的影响。
地塞米松以浓度依赖的方式抑制COPD CD8细胞的细胞因子释放。PDE4抑制剂以累加方式增强了这种抗炎作用。PDE4抑制剂并未增加皮质类固醇诱导的GR核转位。PDE4抑制剂而非皮质类固醇增加了磷酸化CREB的核转位。
皮质类固醇与PDE4抑制剂联合使用对COPD CD8细胞产生累加抗炎作用。这种增强的抗炎作用可能会给COPD患者带来重要的临床益处。
