Norris A A, Jackson D M, Eady R P
Department of Pharmacology, Fisons plc, Loughborough, UK.
Clin Exp Immunol. 1992 Sep;89(3):347-50. doi: 10.1111/j.1365-2249.1992.tb06960.x.
A close association has been recognized between activated T cells and eosinophils in asthma, albeit circumstantial. The present study attempted to investigate this relationship in an animal model of lung eosinophilia using the new generation of T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was assessed by bronchoalveolar lavage. All three agents caused a marked suppression of lung eosinophilia at 24 h post-challenge when the compounds were administered at the time of sensitization but not when administered for 3 days before lavage. However, the lung eosinophilia at 72 h post-challenge was reduced significantly by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were administered for 3 days, before lavage. These results strongly suggest the involvement of T cells in antigen-induced late phase (72 h) eosinophilia in guinea-pigs but not at 24 h. The effects of cyclophosphamide were always associated with a reduction in circulating white cell counts, whereas cyclosporin A and FK506 showed no myelotoxic properties. These results suggest the potential therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.
尽管存在一些间接证据，但人们已经认识到哮喘中活化的T细胞与嗜酸性粒细胞之间存在密切关联。本研究试图在肺部嗜酸性粒细胞增多的动物模型中，使用新一代T细胞选择性免疫抑制剂环孢素A和FK506，并与骨髓毒性免疫抑制剂环磷酰胺进行比较，来研究这种关系。对卵清蛋白致敏的豚鼠进行抗原激发，通过支气管肺泡灌洗评估肺部嗜酸性粒细胞增多情况。当在致敏时给予这三种药物时，在激发后24小时均能显著抑制肺部嗜酸性粒细胞增多，但在灌洗前3天给予则无此效果。然而，当在灌洗前3天给予药物时，FK506和环磷酰胺能显著降低激发后72小时的肺部嗜酸性粒细胞增多，而环孢素A则无此作用。这些结果强烈表明，T细胞参与了豚鼠抗原诱导的晚期（72小时）嗜酸性粒细胞增多，但在24小时时未参与。环磷酰胺的作用总是伴随着循环白细胞计数的减少，而环孢素A和FK506则没有骨髓毒性。这些结果表明选择性、无细胞毒性的免疫抑制剂在哮喘治疗中具有潜在用途。
