Spahn J D, Fost D A, Covar R, Martin R J, Brown E E, Szefler S J, Leung D Y
Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Ann Allergy Asthma Immunol. 2001 Dec;87(6):501-5. doi: 10.1016/S1081-1206(10)62264-8.
Selected macrolide antibiotics have steroid-sparing effects in patients with steroid-dependent asthma. In addition to inhibiting methylprednisolone clearance, macrolides may also display anti-inflammatory effects.
To determine whether clarithromycin, by virtue of its anti-inflammatory effects, enhances glucocorticoid sensitivity.
Open-label, pilot study in a paired design (pre- and posttreatment).
Seven patients, mean age 27 (range 15 to 42 years), with mild to moderate asthma under good control.
Clarithromycin (500 mg) was administered twice daily for 10 days with blood drawn for lymphocyte stimulation assays at baseline, and again upon completion of therapy. Lymphocytes were stimulated with phytohemagglutinin in the presence and absence of increasing concentrations of clarithromycin and dexamethasone (DEX).
At baseline, clarithromycin alone did not cause a significant degree of suppression of T-lymphocyte activation, yet clarithromycin significantly enhanced the sensitivity of lymphocytes to suppression by DEX as measured by a shift in the DEX dose-response curve by at least 6-fold (P = 0.04). In addition, a 10-day course of clarithromycin resulted in: 1) a significant decrease in the inhibitory concentration which results in a 50% reduction in proliferation for DEX alone, thereby increasing glucocorticoid sensitivity (P = 0.04); 2) heightened inhibitory effect of clarithromycin alone (P = 0.03); and 3) a sustained suppressive effect with the combination of clarithromycin and DEX on the inhibition of lymphocyte stimulation (P = 0.01).
Clarithromycin acts synergistically with DEX in suppressing lymphocyte activation. In addition, a 10-day course resulted in a significant treatment effect as evidenced by lower inhibitory concentration which results in a 50% reduction in proliferation value for DEX, a heightened response to clarithromycin alone, and a consistent degree of suppression of lymphocyte stimulation when clarithromycin and DEX were used together.
某些大环内酯类抗生素对激素依赖型哮喘患者具有激素节省效应。除抑制甲泼尼龙清除外，大环内酯类还可能具有抗炎作用。
确定克拉霉素是否因其抗炎作用而增强糖皮质激素敏感性。
配对设计（治疗前和治疗后）的开放标签试点研究。
7例年龄平均27岁（范围15至42岁）、病情得到良好控制的轻至中度哮喘患者。
克拉霉素（500毫克）每日给药2次，共10天，在基线时采集血样用于淋巴细胞刺激试验，治疗结束时再次采血。在存在和不存在浓度递增的克拉霉素和地塞米松（DEX）的情况下，用植物血凝素刺激淋巴细胞。
在基线时，单独使用克拉霉素不会引起T淋巴细胞活化的显著抑制，但通过DEX剂量反应曲线至少6倍的偏移测量，克拉霉素显著增强了淋巴细胞对DEX抑制的敏感性（P = 0.04）。此外，10天的克拉霉素疗程导致：1）单独使用DEX时导致增殖减少50%的抑制浓度显著降低，从而增加糖皮质激素敏感性（P = 0.04）；2）单独使用克拉霉素的抑制作用增强（P = 0.03）；3）克拉霉素和DEX联合对淋巴细胞刺激抑制具有持续的抑制作用（P = 0.01）。
克拉霉素与DEX协同抑制淋巴细胞活化。此外，10天疗程产生了显著的治疗效果，表现为单独使用DEX时导致增殖值减少50%的抑制浓度降低、对单独使用克拉霉素的反应增强以及克拉霉素和DEX联合使用时淋巴细胞刺激的一致抑制程度。
