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

大环内酯类抗生素如曲安霉素(TAO)已被用于治疗重症哮喘。克拉霉素(Clar)是一种新的大环内酯类抗生素，在控制不佳的哮喘患者中的使用频率越来越高。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个核细胞分别与PHA(5 mg/mg)和Clar(1，10，20 mg/ml)共同孵育，加入和不加入地塞米松(Dex)。CLAR(20 mg/ml)单独作用对细胞增殖有抑制作用，与地塞米松共同孵育时有相加作用(表：p=ANOVA O vs 20)。由于大环内酯类药物可以改变糖皮质激素代谢，我们还测定了克拉霉素对甲基强的松龙(MPN)的影响，在治疗前和治疗7d后分别给予PN 40 mg/1.73m2。治疗后MPNCL下降65%(3758+VX 130.0+5ml/min/1.73m2，P=0.003)，而对PNCL无影响(245.0+14ml/min/1.73m2，P=0.003)。我们认为，CLAR单独对Lp有明显的抑制作用，并增强了与Dex的抑制作用。此外，克拉霉素组MPN CL显著降低，但PNCL无明显变化。这种MPN、CL的延迟以及对Lp的影响可能是CLAR对激素依赖型哮喘的有益作用之一。此外，长期接受慢性MPN治疗的患者可能会增加他们发生类固醇不良反应的风险。

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.