de Waal E J, de Jong W H, van der Vliet H, Verlaan B, van Loveren H
National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Int J Immunopharmacol. 1996 Aug-Sep;18(8-9):523-8. doi: 10.1016/s0192-0561(96)00029-x.
Salmeterol, a long-acting beta 2-adrenoreceptor agonist without known immunotoxicity, was studied in a 28-day repeated dose toxicity test in Wistar rats. Several immunotoxicity screening parameters were incorporated in the study protocol to investigate the immunotoxic potential of the compound. Male rats were orally treated with 0, 0.2, 2 and 20 mg salmeterol/kg body weight/day. At the 20 mg/kg/day dose level, intubation errors occurred because the animals tried to resist intubation. Some of these animals died intercurrently. Therefore, the magnitude of the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body weight and bone marrow cellularity were not affected. Hematological parameters were not altered either, except for platelet counts, that were decreased at all dose levels. Also liver weights were decreased at all dose levels tested. Absolute thymic weights were decreased at the 2 and 20/10 mg/kg/day dose levels. No treatment-related (histo)pathological lesions were seen in the (non)lymphoid organs. Serum IgM levels were increased at the 0.2, and IgG at the 2 and 20/10 mg/kg/day dose levels, respectively. B cell numbers in the spleen were decreased at all dose levels tested. The data indicate that the test battery applied to salmeterol is able to detect low immunotoxic potential. Further research is needed to elucidate whether salmeterol interferes with immune responses in rats upon antigenic challenge.
沙美特罗是一种长效β2肾上腺素受体激动剂，尚无已知的免疫毒性。在一项对Wistar大鼠进行的为期28天的重复剂量毒性试验中对其进行了研究。研究方案中纳入了几个免疫毒性筛选参数，以调查该化合物的免疫毒性潜力。雄性大鼠经口给予0、0.2、2和20mg沙美特罗/千克体重/天。在20mg/kg/天的剂量水平，由于动物试图抗拒插管，出现了插管失误。其中一些动物在试验期间死亡。因此，在治疗第9天将剂量降至10mg/kg/天。体重和骨髓细胞数量未受影响。血液学参数也未改变，但所有剂量水平的血小板计数均下降。在所有测试剂量水平下，肝脏重量也下降。在2和20/10mg/kg/天的剂量水平，胸腺绝对重量下降。在（非）淋巴器官中未观察到与治疗相关的（组织）病理学病变。在0.2mg/kg/天剂量水平时血清IgM水平升高，在2和20/10mg/kg/天剂量水平时血清IgG水平分别升高。在所有测试剂量水平下，脾脏中的B细胞数量均下降。数据表明，应用于沙美特罗的测试组合能够检测到低免疫毒性潜力。需要进一步研究以阐明沙美特罗在抗原攻击时是否会干扰大鼠的免疫反应。
