Vuddhakul V, McCormack J G, Seow W K, Thong Y H
Department of Child Health and Medicine, University of Queensland, South Brisbane, Australia.
Int J Immunopharmacol. 1989;11(7):817-28. doi: 10.1016/0192-0561(89)90136-7.
Amphotericin B and some of the imidazole drugs have been shown to suppress certain neutrophil and lymphocyte functions both in vitro and in vivo. We present here the in vitro effects of: amorolfin, a morpholine derivative; the imidazoles clotrimazole and ketoconazole; the N-substituted imidazole bifonazole and a triazole (ICE 195, 739), on neutrophil and lymphocyte function. All of these drugs inhibited neutrophil random migration, chemotaxis and hexose monophosphate shunt activity. The effects of the drugs on neutrophil adherence, deoxyglucose transport and beta-glucuronidase release were variable while lysozyme release was unaffected. Natural Killer cell cytoxicity was depressed by all drugs tested except for amorolfin. Mitogen-induced lymphocyte blastogenesis was suppressed by all the antifungal drugs tested. Similar results were obtained using the mitogens phytohaemagglutinin, concanavalin A and pokeweed mitogen. The mechanism of action of these drugs on these cell functions remains unknown, there may be a correlation between their effects on fungi and their effects on leukocytes. Clearance of systemic fungal infection is heavily dependent on integrity of the cellular immune system and it is clearly undesirable that antifungal drugs have immunosuppressive properties. Further studies are required to determine the in vivo and clinical relevance of our observations.
两性霉素B和一些咪唑类药物已被证实在体外和体内均可抑制某些中性粒细胞和淋巴细胞的功能。我们在此展示了阿莫罗芬（一种吗啉衍生物）、咪唑类药物克霉唑和酮康唑、N-取代咪唑类药物联苯苄唑以及一种三唑类药物（ICE 195, 739）对中性粒细胞和淋巴细胞功能的体外作用。所有这些药物均抑制中性粒细胞的随机迁移、趋化性和磷酸己糖旁路活性。这些药物对中性粒细胞黏附、脱氧葡萄糖转运和β-葡萄糖醛酸酶释放的影响各不相同，而溶菌酶释放则未受影响。除阿莫罗芬外，所有测试药物均降低了自然杀伤细胞的细胞毒性。所有测试的抗真菌药物均抑制有丝分裂原诱导的淋巴细胞母细胞形成。使用植物血凝素、刀豆球蛋白A和商陆有丝分裂原作为有丝分裂原也获得了类似结果。这些药物对这些细胞功能的作用机制尚不清楚，它们对真菌的作用与其对白细胞的作用之间可能存在关联。全身性真菌感染的清除在很大程度上依赖于细胞免疫系统的完整性，抗真菌药物具有免疫抑制特性显然是不可取的。需要进一步研究以确定我们观察结果的体内及临床相关性。
