Adachi T, Motojima S, Hirata A, Fukuda T, Kihara N, Kosaku A, Ohtake H, Makino S
Department of Respiratory Medicine, Kihara Hospital, Tokyo, Japan.
J Allergy Clin Immunol. 1996 Dec;98(6 Pt 2):S207-15. doi: 10.1016/s0091-6749(96)70068-4.
Glucocorticoids have long been used as the most potent drugs in the treatment of bronchial asthma. Data reported recently have led to the proposal that theophylline and macrolides have antiinflammatory effects.
We examined the abilities of theophylline, glucocorticoids, and macrolides to counteract the prolongation of eosinophil survival caused by IL-5.
Purified guinea pig eosinophils were cultured in the presence or absence of human IL-5 and with or without the aforementioned drugs at various concentrations. The percentage of cells alive after 3 days in culture was determined.
Aminophylline (AM), methylprednisolone (MP), erythromycin (EM), and clarithromycin (CAM) suppressed the IL-5 induced prolongation of eosinophil survival in a dose-dependent manner. The effects of these drugs on eosinophil survival were significantly greater at low concentrations of IL-5 than at high concentrations of IL-5. When eosinophils were cultured in the presence of IL-5 (1 ng/ml) with physiologic concentrations of MP (10(-6) mol/L), AM (10(-4) mol/L), and either EM or CAM (both 10 micrograms/ml), the effect of IL-5 was almost completely abolished, and the morphologic changes in eosinophils observed by electron microscopy were consistent with apoptosis. DNA extracted from eosinophils cultured with IL-5 and each of the drugs was definitely fragmented.
One mechanism of the effectiveness of these drugs is induction of eosinophil apoptosis. Some combination of these drugs may be useful in the treatment of bronchial asthma.
长期以来，糖皮质激素一直是治疗支气管哮喘最有效的药物。最近报道的数据提示，茶碱和大环内酯类药物具有抗炎作用。
我们研究了茶碱、糖皮质激素和大环内酯类药物对抗白细胞介素-5（IL-5）所致嗜酸性粒细胞存活时间延长的能力。
将纯化的豚鼠嗜酸性粒细胞在有或无人类IL-5的情况下培养，并添加或不添加不同浓度的上述药物。测定培养3天后存活细胞的百分比。
氨茶碱（AM）、甲泼尼龙（MP）、红霉素（EM）和克拉霉素（CAM）均以剂量依赖方式抑制IL-5诱导的嗜酸性粒细胞存活时间延长。这些药物在低浓度IL-5时对嗜酸性粒细胞存活的影响明显大于高浓度IL-5时。当嗜酸性粒细胞在含有IL-5（1 ng/ml）以及生理浓度的MP（10⁻⁶ mol/L）、AM（10⁻⁴ mol/L）和EM或CAM（均为10 μg/ml）的条件下培养时，IL-5的作用几乎完全被消除，并且通过电子显微镜观察到的嗜酸性粒细胞形态学变化与细胞凋亡一致。从用IL-5和每种药物培养的嗜酸性粒细胞中提取的DNA出现明显片段化。
这些药物发挥作用的一种机制是诱导嗜酸性粒细胞凋亡。这些药物的某些联合应用可能对支气管哮喘的治疗有用。
