Kurup V P, Murali P S, Guo J, Choi H, Banerjee B, Fink J N, Coffman R L
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Allergy. 1997 Dec;52(12):1215-21. doi: 10.1111/j.1398-9995.1997.tb02526.x.
The effect of multiple divided doses compared with single-dose injections of antibodies to murine interleukin (IL)-4 and IL-5 in their respective downregulation of IgE and eosinophilia developing in a model of allergic aspergillosis is investigated. BALB/c mice were exposed to Aspergillus fumigatus antigens (Af) before and along with anticytokine antibodies. The kinetics of blood eosinophils, eosinophil peroxidase (EPO) in bone-marrow cells, serum levels of IgE and Af-specific antibodies, Af-induced cytokine production and mRNA, and lung histology were studied. The results indicate that only multiple anti-IL-5 antibodies were effective in maintaining baseline levels of blood eosinophils. Multiple anti-IL-4 antibodies also downregulated eosinophils in the bone marrow, lung, and peripheral blood, although to a lesser extent than in anti-IL-5 antibody-injected mice. Significant correlation between the EPO activity and the eosinophil numbers in anticytokine antibody-treated mice was observed. The different anti-IL-4 antibody treatments downregulated IgE to the same extent. We conclude that multiple divided doses of anti-IL-5 antibodies are required to sustain normal eosinophil levels in murine allergic aspergillosis. This information may be significant in the therapy of pulmonary allergic diseases.
研究了在变应性曲霉病模型中，与单剂量注射抗小鼠白细胞介素（IL）-4和IL-5抗体相比，多次分剂量注射这些抗体在各自下调IgE和嗜酸性粒细胞增多方面的效果。在接触抗细胞因子抗体之前及同时，将BALB/c小鼠暴露于烟曲霉抗原（Af）。研究了血液嗜酸性粒细胞的动力学、骨髓细胞中的嗜酸性粒细胞过氧化物酶（EPO）、IgE和Af特异性抗体的血清水平、Af诱导的细胞因子产生和mRNA以及肺组织学。结果表明，只有多次注射抗IL-5抗体才能有效维持血液嗜酸性粒细胞的基线水平。多次注射抗IL-4抗体也能下调骨髓、肺和外周血中的嗜酸性粒细胞，尽管程度低于注射抗IL-5抗体的小鼠。在抗细胞因子抗体治疗的小鼠中，观察到EPO活性与嗜酸性粒细胞数量之间存在显著相关性。不同的抗IL-4抗体治疗对IgE的下调程度相同。我们得出结论，在小鼠变应性曲霉病中，需要多次分剂量注射抗IL-5抗体来维持正常的嗜酸性粒细胞水平。这一信息可能对肺部变应性疾病的治疗具有重要意义。
