西洛司特对COPD患者PBMC分泌IL-8和TNF-α的影响

Effect of cilomilast on IL-8 and TNF-α release by peripheral blood mononuclear cells in COPD patients

目的研究西洛司特在体外对COPD患者PBMC分泌IL-8和TNF-α的影响。方法从12例COPD患者外周血中分离的单个核细胞(PBMC)分别与不同浓度的西洛司特、氨茶碱和甲基强的松龙共培养24 h,用ELISA的方法检测PBMC培养上清的IL-8和TNF-α水平。结果西洛司特和氨茶碱对PBMC分泌IL-8和TNF-α均呈显著的浓度依赖性抑制作用(P<0.01)。甲基强的松龙对PBMC分泌IL-8和TNF-α则无显著抑制作用。1μmol/L的西洛司特使LPS刺激PBMC活化分泌的IL-8减少54%,15μg/m l的氨茶碱可使其减少39%,两者在治疗剂量所能达到的血药浓度比较有显著性差异(P<0.01)。1μmol/L的西洛司特使LPS刺激PBMC活化分泌的TNF-α减少51%,15μg/m l的氨茶碱可使其减少32%,两者在治疗剂量所能达到的血药浓度比较有显著性差异(P<0.01)。结论西洛司特和氨茶碱在体外可显著地抑制抑制PBMC分泌IL-8和TNF-α,且西洛司特的抑制作用显著强于氨茶碱,甲基强的松龙这种抗炎作用不明显,提示西洛司特对COPD患者有显著的抗炎活性,具有广阔的临床应用前景。

Objective To investigate the effect of cilomilast on IL-8 and TNF-α release by peripheral blood mononuclear cells （PBMC） in patients with chronic obstructive pulmonary disease （COPD）. Methods Peripheral blood mononuclear cells （PBMC） separated from blood of COPD patients were cultured in the presence of different concentrations of cilomilast, methylprednisolone and aminophylline for 24 h. After the incubation the absolute values of IL-8 and TNF-α in supernatants were assessed using ELISA. The effects on IL-8 and TNF-α of different drugs and different concentrations were compared. Results All three concentrations of cilomilast （0.1,1,10μmol/L） and aminophylline （5, 15, 25μg/ml） significantly reduced IL-8 and TNF-α release by PBMC（P 〈0.01）. But all three concentrations of methylprednisolone （0.05, 0. 10, 0. 15 μmol/L） did not significantly reduce IL-8 and TNF-α release by PBMC. Cilomilast （1 μmol/L） reduced the release of IL-8 by 54% and aminophylline （15 μg/ml） , by 39% （P 〈0.01）. Cilomilast （1 μmol/L） reduced the release of TNF-α by 51% and aminophylline （15 μg/ml） , by 32% （P 〈0.01 ）. Conclusion Cilomilast and aminophylline significantly reduce IL-8 and TNF-α release by PBMC in vitro, and the effect of cilomilast on IL- 8 and TNF-α is stronger than that of aminophylline, but methylprednisolone has no such anti-inflammation effect. Cilomilast is effective on airway inflammation of COPD and has broad clinical prospect.