Van Oosterhout A J, Ladenius A R, Savelkoul H F, Van Ark I, Delsman K C, Nijkamp F P
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
Am Rev Respir Dis. 1993 Mar;147(3):548-52. doi: 10.1164/ajrccm/147.3.548.
Chronic ovalbumin challenge of sensitized guinea pigs induces bronchoalveolar lavage (BAL) eosinophilia, neutrophilia, and tracheal hyperreactivity. In the present study, the influence of monoclonal antibody to murine interleukin-5 (anti-IL-5) on these phenomena is examined. In ovalbumin-sensitized guinea pigs treated with isotype-matched control antibody and challenged daily with ovalbumin for 8 days, the number of BAL eosinophils and neutrophils is increased significantly six- and fivefold, respectively, compared with saline-challenged animals. The maximal contractions of tracheal rings to histamine and arecoline in ovalbumin-challenged animals are enhanced significantly to 155% compared with saline-challenged animals. In sensitized guinea pigs treated with anti-IL-5, the BAL eosinophil number is markedly inhibited compared with control antibody treatment in both saline- and ovalbumin-challenged animals. In contrast, the number of neutrophils is not affected by anti-IL-5 treatment. In guinea pigs treated with anti-IL-5, the development of hyperreactivity to histamine and arecoline after ovalbumin challenge is completely inhibited. The contractions to histamine and arecoline of tracheal rings isolated from guinea pigs treated with recombinant murine IL-5 for 3 or 7 days are enhanced significantly to approximately 140% compared with controls. Treatment with IL-5 for 7 days tends to increase the number of eosinophils in BAL fluid. It can be concluded that IL-5 is involved in airway eosinophilia and in the development of hyperreactivity in this animal model, but other cytokines may contribute. Development of IL-5 synthesis inhibitors and/or receptor antagonists could provide another therapeutic class of anti-asthma drugs.
对致敏豚鼠进行慢性卵清蛋白激发会导致支气管肺泡灌洗（BAL）嗜酸性粒细胞增多、中性粒细胞增多以及气管高反应性。在本研究中，检测了抗小鼠白细胞介素-5单克隆抗体（抗IL-5）对这些现象的影响。在用同型对照抗体处理并每日用卵清蛋白激发8天的卵清蛋白致敏豚鼠中，与用生理盐水激发的动物相比，BAL嗜酸性粒细胞和中性粒细胞的数量分别显著增加了6倍和5倍。与用生理盐水激发的动物相比，卵清蛋白激发动物的气管环对组胺和槟榔碱的最大收缩显著增强至155%。在用抗IL-5处理的致敏豚鼠中，与生理盐水激发和卵清蛋白激发动物中的对照抗体处理相比，BAL嗜酸性粒细胞数量明显受到抑制。相比之下，中性粒细胞数量不受抗IL-5处理的影响。在用抗IL-5处理的豚鼠中，卵清蛋白激发后对组胺和槟榔碱的高反应性发展被完全抑制。与对照组相比，用重组小鼠IL-5处理3天或7天的豚鼠分离的气管环对组胺和槟榔碱的收缩显著增强至约140%。用IL-5处理7天倾向于增加BAL液中嗜酸性粒细胞的数量。可以得出结论，IL-5参与了该动物模型中的气道嗜酸性粒细胞增多和高反应性的发展，但其他细胞因子可能也起作用。开发IL-5合成抑制剂和/或受体拮抗剂可能会提供另一类抗哮喘治疗药物。
