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低剂量干扰素-α治疗对糖皮质激素抵抗型哮喘患者的临床及免疫学影响

Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma.

作者信息

Simon H-U, Seelbach H, Ehmann R, Schmitz M

机构信息

Department of Pharmacology, University of Bern, Bern High-Altitude Clinic Davos-Wolfgang, Davos, Switzerland.

出版信息

Allergy. 2003 Dec;58(12):1250-5. doi: 10.1046/j.1398-9995.2003.00424.x.

Abstract

BACKGROUND

Interferon (IFN)-alpha is a cytokine that possesses potent anti-viral and immunoregulatory activities. We aimed to assess clinical and immunological effects of low-dose IFN-alpha in patients with severe corticosteroid-resistant asthma with and without Churg-Strauss syndrome. There is currently no efficient pharmacological treatment available for this group of patients.

METHODS

We studied 10 patients with corticosteroid-resistant asthma, in which 3x10(6) IU/day IFN-alpha were administrated in addition to the prednisone dose given already before introduction of the cytokine therapy. The prednisone dose was gradually reduced dependent on the clinical situation and used as a clinical readout to evaluate the efficacy of the cytokine therapy. To distinguish between IFN-alpha- and prednisone-mediated immunological changes, the corticosteroid dose was kept constant for at least 2 weeks upon introduction of the cytokine therapy in seven patients. The effects of treatment on clinical and immunological parameters were measured at 2-4 weeks and 5-10 months depending on the availability of the patient.

RESULTS

Interferon-alpha treatment rapidly improved the clinical situation as assessed by lung function parameters and required prednisone dose. Important immunological changes included: decreased leukocyte numbers, increased relative numbers of CD4+ T cells, increased differentiation of T helper (Th)1 cells, and increased expression of interleukin (IL)-10 in peripheral blood mononuclear cells.

CONCLUSION

Interferon-alpha treatment was associated with dramatic improvements in the condition of patients with corticosteroid-resistant asthma with and without Churg-Strauss syndrome. Potential mechanisms of action include the establishment of a correct Th1/Th2 balance and the induction of the anti-inflammatory IL-10 gene.

摘要

背景

干扰素(IFN)-α是一种具有强大抗病毒和免疫调节活性的细胞因子。我们旨在评估低剂量IFN-α对伴有或不伴有Churg-Strauss综合征的严重糖皮质激素抵抗性哮喘患者的临床和免疫学影响。目前尚无针对该组患者的有效药物治疗方法。

方法

我们研究了10例糖皮质激素抵抗性哮喘患者,在细胞因子治疗开始前,除了已给予的泼尼松剂量外,每天给予3×10⁶IU的IFN-α。泼尼松剂量根据临床情况逐渐减少,并用作评估细胞因子治疗疗效的临床指标。为了区分IFN-α和泼尼松介导的免疫学变化,在7例患者引入细胞因子治疗后,将糖皮质激素剂量至少维持2周不变。根据患者的情况,在2-4周和5-10个月时测量治疗对临床和免疫学参数的影响。

结果

通过肺功能参数和所需泼尼松剂量评估,IFN-α治疗迅速改善了临床状况。重要的免疫学变化包括:白细胞数量减少、CD4⁺T细胞相对数量增加、辅助性T(Th)1细胞分化增加以及外周血单个核细胞中白细胞介素(IL)-10表达增加。

结论

IFN-α治疗使伴有或不伴有Churg-Strauss综合征的糖皮质激素抵抗性哮喘患者的病情显著改善。潜在的作用机制包括建立正确的Th1/Th2平衡和诱导抗炎性IL-10基因。

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