Heijink Irene H, Kauffman Henk F, Vellenga Edo, Veltman-Starkenburg Christa A, Postma Dirkje S, de Monchy Jan G R
Department of Allergology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Int Arch Allergy Immunol. 2008;145(2):111-21. doi: 10.1159/000108136. Epub 2007 Sep 10.
The allergen-induced release of CCL17/thymus and activation-regulated chemokine (TARC) may be crucial in asthmatic airway inflammation by recruitment of Th2 cells. In addition, it might lead to aberrant Th2 cell activity through impairment of beta2-adrenergic receptor (beta2-AR) control. We questioned how chemokine patterns change upon allergen challenge and whether treatment with the inhaled steroid ciclesonide can reduce chemokine release and subsequently prevent allergen-induced changes in Th2 cell regulation and migration.
Asthma patients were double-blindly treated with placebo or 80 microg ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of beta2-agonist fenoterol over T cell migration and alpha-CD3/alpha-CD28-induced cytokine production.
Treatment with 80 microg ciclesonide significantly diminished the late asthmatic response. The late asthmatic response was associated with increased sputum levels of CCL17 and CCL4 (but none of the other chemokines measured) and loss of beta2-AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered beta2-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and alpha-CD3/alpha-CD28-induced cytokine production.
Our data support the hypothesis that CCL17 is involved in allergen-induced dysregulation of Th2 cell migration and cytokine production. Ciclesonide treatment inhibits T cell migration and cytokine production upon allergen inhalation, which is regulated independently from reducing CCL17 release, but may contribute to beneficial effects of ciclesonide on Th2-mediated airway inflammation.
变应原诱导的CCL17/胸腺激活调节趋化因子（TARC）释放可能通过募集Th2细胞在哮喘气道炎症中起关键作用。此外，它可能通过损害β2肾上腺素能受体（β2-AR）控制导致Th2细胞异常活动。我们想知道变应原激发后趋化因子模式如何变化，以及吸入性糖皮质激素环索奈德治疗是否能减少趋化因子释放，进而预防变应原诱导的Th2细胞调节和迁移变化。
哮喘患者被双盲给予安慰剂或80微克环索奈德治疗7天。我们研究了变应原诱导的痰液趋化因子变化、外周血T细胞迁移以及β2激动剂非诺特罗对T细胞迁移和α-CD3/α-CD28诱导的细胞因子产生的控制。
80微克环索奈德治疗显著减轻了迟发性哮喘反应。迟发性哮喘反应与痰液中CCL17和CCL4水平升高（但未检测到其他趋化因子）以及β2-AR对T细胞迁移和Th2型细胞因子产生的控制丧失有关。虽然环索奈德治疗不能预防趋化因子释放，也未改变循环T细胞中的β2-AR功能，但它对TARC诱导的T细胞迁移和α-CD3/α-CD28诱导的细胞因子产生具有抑制作用。
我们的数据支持CCL17参与变应原诱导的Th2细胞迁移和细胞因子产生失调这一假说。环索奈德治疗可抑制变应原吸入时的T细胞迁移和细胞因子产生，这一作用独立于减少CCL17释放，但可能有助于环索奈德对Th2介导的气道炎症产生有益作用。
