Hellman C, Lönnkvist K, Hedlin G, Halldén G, Lundahl J
Department of Medicine, Division of Clinical Immunology and Allergy, Stockholm, Sweden.
Allergy. 2002 Apr;57(4):323-8. doi: 10.1034/j.1398-9995.2002.1o3482.x.
The expression and function of cytokine receptors on peripheral blood eosinophils (PBE) from healthy and asthmatic children are poorly characterized.
The PBE count and expression of IL-5 receptor (R) and GM-CSFR positive PBE was analyzed in nonsteroid-treated asthmatic children (n = 13), budesonide-treated asthmatic children (n = 24) and healthy children (n = 16) by flow cytometry. Alterations in intracellular EG2-epitope expression were used to measure the in vitro responsiveness of PBE to recombinant IL-5 and GM-CSF.
The PBE count was increased (P < 0.05) in both asthmatic groups, independent of treatment, as compared to healthy children. The IL-5R expression on PBE, as well as the in vitro responsiveness of PBE to recombinant IL-5, was reduced (P < 0.05), in budesonide-treated asthmatic children compared to nonsteroid-treated asthmatic children and healthy children. The proportion of GM-CSFR positive PBE and in vitro responsiveness of PBE to recombinant GM-CSF were not different between the groups. In vitro treatment with budesonide did not down-regulate the proportion of IL-5R positive PBE.
Budesonide-treatment of asthmatic children induces a selectively reduced IL-5R expression on PBE, concomitant with a reduced in vitro responsiveness of PBE to IL-5. We suggest that this budesonide-related down-regulation of the IL-5R might be a mechanism by which steroid treatment inhibits the action of IL-5 on eosinophil accumulation and activation in vivo.
健康儿童和哮喘儿童外周血嗜酸性粒细胞(PBE)上细胞因子受体的表达及功能尚未得到充分表征。
通过流式细胞术分析未接受类固醇治疗的哮喘儿童(n = 13)、布地奈德治疗的哮喘儿童(n = 24)和健康儿童(n = 16)的PBE计数以及IL-5受体(R)和GM-CSFR阳性PBE的表达。细胞内EG2表位表达的变化用于测量PBE对重组IL-5和GM-CSF的体外反应性。
与健康儿童相比,两个哮喘组的PBE计数均增加(P < 0.05),且与治疗无关。与未接受类固醇治疗的哮喘儿童和健康儿童相比,布地奈德治疗的哮喘儿童PBE上的IL-5R表达以及PBE对重组IL-5的体外反应性降低(P < 0.05)。各组之间GM-CSFR阳性PBE的比例以及PBE对重组GM-CSF的体外反应性没有差异。布地奈德体外治疗并未下调IL-5R阳性PBE的比例。
布地奈德治疗哮喘儿童可导致PBE上IL-5R表达选择性降低,同时PBE对IL-5的体外反应性降低。我们认为,布地奈德相关的IL-5R下调可能是类固醇治疗抑制IL-5在体内对嗜酸性粒细胞聚集和激活作用的一种机制。