Bruijnzeel P L, Warringa R A, Kok P T, Hamelink M L, Kreukniet J
Department of Pulmonary Disease, State University Hospital Utrecht, The Netherlands.
Drugs. 1989;37 Suppl 1:9-18; discussion 69-77. doi: 10.2165/00003495-198900371-00004.
Inflammatory cells, such as neutrophils and eosinophils, are thought to actively contribute to the pathogenesis of asthma since they infiltrate into the lung tissue and may be activated locally to release bronchoconstrictor mediators. In this study we provide evidence that nedocromil sodium is capable of effectively inhibiting the platelet-activating factor (PAF) and zymosan-activated serum (ZAS)-induced chemotaxis of polymorphonuclear granulocytes (PMN) [IC50 approximately 1 nmol/L and 0.1 mumol/L respectively]. The same inhibitory potency was obtained with sodium cromoglycate. Thus, nedocromil sodium may effectively inhibit the mobilisation of inflammatory cells in the lung. Furthermore, nedocromil sodium is capable of inhibiting the formation of the bronchoconstrictor mediator leukotriene-C4 (LTC4) by eosinophils in a concentration-dependent way [IC30 for A23187: 5.6 10(-5) mol/L; IC30 for opsonised zymosan (OZ): 6.3 10(-5) mol/L], whereas this drug is not capable of inhibiting leukotriene-B4 (LTB4) formation by neutrophils. These findings indicate that nedocromil sodium inhibits the release of bronchoconstrictor mediators not only from mast cells but also from eosinophils.
炎症细胞，如中性粒细胞和嗜酸性粒细胞，被认为在哮喘发病机制中发挥积极作用，因为它们可浸润到肺组织中，并可能在局部被激活，释放支气管收缩介质。在本研究中，我们提供证据表明，奈多罗米钠能够有效抑制血小板活化因子（PAF）和酵母聚糖激活血清（ZAS）诱导的多形核粒细胞（PMN）趋化作用[IC50分别约为1 nmol/L和0.1 μmol/L]。色甘酸钠也具有相同的抑制效力。因此，奈多罗米钠可能有效抑制肺内炎症细胞的动员。此外，奈多罗米钠能够以浓度依赖的方式抑制嗜酸性粒细胞形成支气管收缩介质白三烯C4（LTC4）[A23187的IC30：5.6×10⁻⁵ mol/L；调理酵母聚糖（OZ）的IC30：6.3×10⁻⁵ mol/L]，而该药物不能抑制中性粒细胞形成白三烯B4（LTB4）。这些发现表明，奈多罗米钠不仅抑制肥大细胞释放支气管收缩介质，还抑制嗜酸性粒细胞释放该介质。
