Fukuda T, Asakawa J, Motojima S, Makino S
Department of Internal Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan.
Ann Allergy Asthma Immunol. 1995 Jul;75(1):65-72.
Although cyclosporine A is proving effective for chronic severe asthma, its mechanism of action in this disease is unclear.
This open study was conducted to determine whether cyclosporine A therapy would reduce the degree of airway hyperresponsiveness and T lymphocyte activity.
After a 6-week run-in period, nine patients with corticosteroid-dependent chronic severe asthma were treated with cyclosporine A (initial dose 5 mg/kg per day) for 12 weeks.
Weekly mean morning peak expiratory flow significantly increased in six subjects during the last 6 weeks of trial. Geographic mean PC20-acetylcholine (the provocative concentration of acetylcholine required to cause a 20% fall in FEV1) was 0.147 mg/mL before cyclosporine A treatment and increased to 0.216 mg/mL at 6 weeks and to 0.379 mg/mL at 12 weeks after treatment. The increase at 12 weeks was statistically significant (P < .05). The percentage of CD4-positive T lymphocytes bearing IL-2 receptor (a marker of T cell activation) in the peripheral blood decreased significantly at 6 weeks (P < .05), but returned to baseline value at 12 weeks, probably due to cyclosporine A dose reduction in seven subjects. Serum IgE levels and peripheral blood eosinophil counts, however, which are dependent on IL-4 and IL-5, respectively, were still significantly decreased at 12 weeks, suggesting lymphokine production remained suppressed even after cyclosporine A dose was reduced.
Taken together, these data suggest that cyclosporine A may act in asthma, at least in part, by inhibition of T lymphocyte activation and by reducing the degree of airway hyperresponsiveness.
尽管环孢素A已被证明对慢性重度哮喘有效，但其在该疾病中的作用机制尚不清楚。
进行这项开放性研究以确定环孢素A治疗是否会降低气道高反应性程度和T淋巴细胞活性。
经过6周的导入期后，9例依赖皮质类固醇的慢性重度哮喘患者接受环孢素A治疗（初始剂量为每日5 mg/kg），为期12周。
在试验的最后6周，6名受试者的每周平均晨起呼气峰流量显著增加。环孢素A治疗前，乙酰甲胆碱激发试验的PC20（使第一秒用力呼气容积下降20%所需的乙酰甲胆碱激发浓度）的几何平均值为0.147 mg/mL，治疗6周时升至0.216 mg/mL，治疗12周时升至0.379 mg/mL。12周时的升高具有统计学意义（P < 0.05）。外周血中携带白细胞介素-2受体的CD4阳性T淋巴细胞百分比（T细胞活化标志物）在6周时显著下降（P < 0.05），但在12周时恢复至基线值，这可能是由于7名受试者的环孢素A剂量减少。然而，分别依赖白细胞介素-4和白细胞介素-5的血清免疫球蛋白E水平和外周血嗜酸性粒细胞计数在12周时仍显著降低，这表明即使环孢素A剂量减少，淋巴因子的产生仍受到抑制。
综上所述，这些数据表明环孢素A在哮喘中的作用可能至少部分是通过抑制T淋巴细胞活化和降低气道高反应性程度来实现的。
