Warringa R A, Mengelers H J, Maikoe T, Bruijnzeel P L, Koenderman L
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
J Allergy Clin Immunol. 1993 Mar;91(3):802-9. doi: 10.1016/0091-6749(93)90200-y.
Eosinophil influx into the lung tissue is considered to be relevant for the pathogenesis of asthma. Various chemotactic factors may be responsible for this influx. Recently it has been demonstrated that the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5) are present in the circulation of individuals with allergic asthma. These cytokines have the capacity to modulate chemotactic responses of eosinophils toward platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, (FMLP) and neutrophil-activating factor (NAF)/IL-8, but not toward complement fragment C5a (C5a). Here the effect of nedocromil sodium on the chemotactic response of eosinophils from allergic asthmatic individuals and from normal donors preincubated with GM-CSF or IL-3 toward FMLP, NAF/IL-8 was evaluated.
Nedocromil sodium inhibited the chemotactic response toward FMLP and NAF/IL-8 of GM-CSF primed eosinophils approximately 60% (inhibitory concentration of 50% [IC50] approximately 1 to 10 nmol/L), whereas these responses of IL-3 primed eosinophils was completely inhibited (IC50 approximately 1 nmol/L).
The chemotactic responses toward C5a were inhibited by nedocromil sodium at higher concentrations than were required in the priming studies (IC50 approximately 10 to 100 nmol/L). Nedocromil sodium (0.1 mumol/L) was also effective in inhibiting the chemotactic response toward FMLP (10 nmol/L) of eosinophils isolated from the circulation of patients with allergic asthma 3 hours after allergen challenge. These findings might explain in part the antiinflammatory action of nedocromil sodium.
嗜酸性粒细胞流入肺组织被认为与哮喘的发病机制相关。多种趋化因子可能导致这种流入。最近已证实，粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）、白细胞介素 - 3（IL - 3）和白细胞介素 - 5（IL - 5）细胞因子存在于过敏性哮喘患者的循环中。这些细胞因子能够调节嗜酸性粒细胞对血小板活化因子、甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）和中性粒细胞活化因子（NAF）/白细胞介素 - 8的趋化反应，但对补体片段C5a（C5a）无此作用。在此评估了奈多罗米钠对来自过敏性哮喘患者和预先用GM - CSF或IL - 3孵育的正常供体的嗜酸性粒细胞对FMLP、NAF/IL - 8趋化反应的影响。
奈多罗米钠抑制GM - CSF预致敏嗜酸性粒细胞对FMLP和NAF/IL - 8的趋化反应约60%（50%抑制浓度[IC50]约为1至10 nmol/L），而IL - 3预致敏嗜酸性粒细胞的这些反应则被完全抑制（IC50约为1 nmol/L）。
奈多罗米钠抑制对C5a的趋化反应所需浓度高于预致敏研究中的浓度（IC50约为10至100 nmol/L）。奈多罗米钠（0.1 μmol/L）在抑制变应原激发3小时后从过敏性哮喘患者循环中分离出的嗜酸性粒细胞对FMLP（10 nmol/L）的趋化反应方面也有效。这些发现可能部分解释了奈多罗米钠的抗炎作用。
