Mullol J, López E, Roca-Ferrer J, Xaubet A, Pujols L, Fernàndez-Morata J C, Fabra J M, Picado C
Fundació Clínic per a la Recerca Biomèdica, Hospital Clínic i Universitari, Departament de Medicina, Universitat de Barcelona, Spain.
Clin Exp Allergy. 1997 Dec;27(12):1432-41.
Eosinophil infiltration is a hallmark of the inflammatory response in rhinitis and in nasal polyposis.
We studied the effect of steroids and nedocromil sodium on eosinophil survival primed by epithelial cells from healthy (nasal mucosa) and inflamed (nasal polyp) respiratory tissue.
Blood eosinophils were incubated with increasing concentrations (10(-11)-10(-5) M) of topical steroids (fluticasone propionate, budesonide, triamcinolone acetonide and beclomethasone dipropionate) and/or nedocromil sodium prior to the addition of human epithelial cell conditioned media (HECM), eosinophil viability was measured and IC50 for each drug was calculated.
All four steroids and nedocromil sodium caused a dose-related inhibition of HECM-induced eosinophil survival. The IC50 of steroids were lower in eosinophils primed by mucosa HECM than on those primed by polyp HECM (fluticasone, 4 nM vs 114 nM; budesonide, 21 nM vs 280 nM; triamcinolone, 7 nM vs 853 nM; and beclomethasone, 171 nM vs 181 nM). The combined inhibitory effect of 10(-7) M budesonide plus 10(-5) M nedocromil (43.8 +/- 10.8%, P<0.03) was significantly higher than budesonide (28.5 +/- 9.2%) or nedocromil (16.7 +/- 5.4%) alone and close to 10(-5) M budesonide (52.3 +/- 11%). No differences were found in cytokine (IL-8, IL-6, GM-CSF, TNF alpha, IL-1beta and RANTES) concentrations between HECM from mucosa and polyps.
These results suggest that topical anti-inflammatory drugs may diminish airway eosinophilic infiltration by decreasing eosinophil viability, that nasal polyp epithelial cell secretions may induce steroid resistance in eosinophils, and that nedocromil sodium has additive effects with steroids.
嗜酸性粒细胞浸润是鼻炎和鼻息肉炎症反应的一个标志。
我们研究了类固醇和奈多罗米钠对由健康（鼻黏膜）和发炎（鼻息肉）呼吸组织的上皮细胞引发的嗜酸性粒细胞存活的影响。
在添加人上皮细胞条件培养基（HECM）之前，将血液嗜酸性粒细胞与浓度递增（10⁻¹¹ - 10⁻⁵ M）的局部用类固醇（丙酸氟替卡松、布地奈德、曲安奈德和二丙酸倍氯米松）和/或奈多罗米钠一起孵育，测量嗜酸性粒细胞活力并计算每种药物的半数抑制浓度（IC50）。
所有四种类固醇和奈多罗米钠均引起与剂量相关的对HECM诱导的嗜酸性粒细胞存活的抑制。黏膜HECM引发的嗜酸性粒细胞中类固醇的IC50低于息肉HECM引发的嗜酸性粒细胞中的IC50（丙酸氟替卡松，4 nM对114 nM；布地奈德，21 nM对280 nM；曲安奈德，7 nM对853 nM；二丙酸倍氯米松，171 nM对181 nM）。10⁻⁷ M布地奈德加10⁻⁵ M奈多罗米的联合抑制作用（43.8±10.8%，P<0.03）显著高于单独使用布地奈德（28.5±9.2%）或奈多罗米（16.7±5.4%），且接近10⁻⁵ M布地奈德（52.3±11%）。鼻黏膜和鼻息肉的HECM之间细胞因子（IL - 8、IL - 6、GM - CSF、TNFα、IL - 1β和RANTES）浓度未发现差异。
这些结果表明，局部抗炎药物可能通过降低嗜酸性粒细胞活力来减少气道嗜酸性粒细胞浸润，鼻息肉上皮细胞分泌物可能诱导嗜酸性粒细胞产生类固醇耐药性，并且奈多罗米钠与类固醇有相加作用。
