NON ANTIMICROBIAL ACTIONS OF CLARITHYROMYCIN (BIAXIN) IN ADULTS WITH ASTHMA

大环内酯类抗生素如曲莱霉素（TAO）已被用于治疗严重哮喘。克拉霉素（Clar）是一种新的大环内酯类抗生素，用于控制不良的哮喘患者的频率越来越高。因此，我们试图通过测量其抑制pha诱导的淋巴细胞增殖（LP）的能力来确定Clar是否具有抗炎作用。5例哮喘患者外周血单核细胞与PHA （5mg /mg）和Clar（1,10和20mg/ml）共孵育，分别在有或没有增加地塞米松（Dex）浓度的情况下孵育。单独使用克拉霉素（20mg /ml）可抑制细胞增殖，当克拉霉素与Dex共孵育时可观察到加性效应（p=ANOVA 0 vs . 20）。由于大环内酯类药物可以改变糖皮质激素的代谢，我们还测定了克拉霉素对甲基强的松龙（MPn）的影响，在克拉霉素治疗7 d前后分别测定了MPn 40 mg/1.73 m2。Clar治疗导致MPn CL降低65% (375 8+ vx 130.0 +5ml/min/1.73 m2;p=0.003)，而对Pn CL没有影响（238.5+17 vs 245.0+14 ml/min/1.73 m2）。我们得出结论，Clar对LP有明显的抑制作用，并增强了对Dex的抑制作用。此外，克拉霉素治疗可显著降低MPn CL，但不能降低PN CL。这种MPn、CL的延迟以及对LP的影响可能有助于Clar对类固醇依赖性哮喘的有益作用。此外，接受慢性MPn治疗的患者长期使用Clar可能会增加他们发生类固醇引起的不良反应的风险。

Macrolide antibiotics such as troleandomycin (TAO) have been used in the treatment of severe asthma. Clarithromycin (Clar), a new macrolide antibiotic, is being used with increasing frequency in patients with poorly controlled asthma. We thus sought to determine whether Clar displays anti-inflammatory effects by measuring its ability to suppress PHA-induced lymphocyte proliferation (LP). Peripheral blood mononuclear cells from 5 asthmatics were co-incubated with PHA (5 mg/mg) & Clar (1,10, and 20mg/ml) in the presence and absence of increasing concentrations of Dexamethasone (Dex). Clar (20 mg/ml) alone resulted in suppression of proliferation, & an additive effect was noted when Clarithromycin was co-incubated with Dex (table; p=ANOVA O vs 20). Since macrolides can alter glucocorticoid metabolism, we also determined the effect of Clarithromycin on methylprednisolone (MPn), Pn 40 mg/1.73 m2) were perfermed prior to & after a 7 d course of Clar. Clar therapy resulted in a 65% reduction in MPn CL (375 8+ vx 130.0 +5ml/min/1.73 m2;p=0.003) while having no effect on Pn CL (238.5+17 vs. 245.0+14 ml/min/1.73 m2). We conclude that Clar causes significant inhibitation of LP alone and amplifies the inhabitation with Dex. In addition, Clarithromycin therapy results in a significant reduction in MPn CL but not PN cl. This delay in MPn, CL, along with the effect on LP may contribute to the beneficial effects of Clar in steroid dependent asthma. In addition, long-term Clar therapy in patients on chronic MPn therapy may increase their risk for steroid-induced adverse effects.