Savolainen J, Jacobsen L, Valovirta E
Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland.
Allergy. 2006 Oct;61(10):1184-90. doi: 10.1111/j.1398-9995.2006.01206.x.
During subcutaneous immunotherapy (SCIT), there is a local mucosal shift from Th2 to Th1 type cytokine predominance and downregulation of interleukin (IL)-5 and eosinophilia. According to recent studies IL-10- and transforming growth factor (TGF)-beta-induced tolerance is another key phenomenon in SCIT. Few data to date is available on mechanisms and roles of these cytokines in sublingual immunotherapy (SLIT).
This study was undertaken to analyse the allergen-induced in vitro mRNA expression of IL-4, IL-5, IL-10, TGF-beta and interferon (IFN)-gamma during SLIT in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR).
Ten patients with AR undergoing pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with a weekly dose of 24,000 SQ-U of glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included in the study. Peripheral blood mononuclear cell samples were collected and stimulated with pollen allergen extract prior to the treatment, after 1 and 2 years of the treatment. The cytokine mRNA expression was assessed using kinetic real time reverse transcription polymerase chain reaction (RT-PCR; TaqMan).
The in vitro allergen-induced mRNA expression of IL-5 by PBMC in the placebo group at 1 (P = 0.0065) and 2 (P = 0.013) years of therapy were increased in comparison with the highest dose. The expression of IL-10 mRNA was increased in the highest dose group (P = 0.0016) and the lower dose group (P = 0.034) at 2 years of therapy when compared with placebo. The change in the expression of allergen-induced TGF-beta had an inversed correlation with the change of IL-5 (r = -0.38, P = 0.036) and positive correlation with the change of IL-10 (r = 0.58, P = 0.0019).
Sublingual immunotherapy induced a dose-dependent systemic allergen-specific immunological response in children with AR. During high-dose SLIT, there was activation of regulatory cytokine IL-10 and an inhibitory effect on IL-5 expression increase that was associated with TGF-beta.
在皮下免疫疗法(SCIT)期间,局部黏膜存在从以Th2型细胞因子占主导向Th1型细胞因子占主导的转变,同时白细胞介素(IL)-5下调且嗜酸性粒细胞减少。根据最近的研究,IL-10和转化生长因子(TGF)-β诱导的耐受性是SCIT中的另一个关键现象。迄今为止,关于这些细胞因子在舌下免疫疗法(SLIT)中的机制和作用的数据很少。
本研究旨在分析变应原诱导的变应性鼻炎(AR)患儿外周血单个核细胞(PBMC)在SLIT期间白细胞介素-4(IL-4)、IL-5、IL-10、TGF-β和干扰素(IFN)-γ的体外mRNA表达。
本研究纳入10例接受花粉SLIT治疗的AR患者,每周剂量为200,000 SQ-U;10例接受疣桦、榛和桤木甘油化混合物每周剂量为24,000 SQ-U的治疗;10例接受安慰剂治疗。在治疗前、治疗1年和2年后采集外周血单个核细胞样本,并用花粉变应原提取物进行刺激。使用实时定量逆转录聚合酶链反应(RT-PCR;TaqMan)评估细胞因子mRNA表达。
与最高剂量组相比,安慰剂组在治疗1年(P = 0.0065)和2年(P = 0.013)时PBMC体外变应原诱导的IL-5 mRNA表达增加。与安慰剂相比,在治疗2年时,最高剂量组(P = 0.0016)和较低剂量组(P = 0.034)的IL-10 mRNA表达增加。变应原诱导的TGF-β表达变化与IL-5变化呈负相关(r = -0.38,P = 0.036),与IL-10变化呈正相关(r = 0.58,P = 0.0019)。
舌下免疫疗法在AR患儿中诱导了剂量依赖性的全身变应原特异性免疫反应。在高剂量SLIT期间,调节性细胞因子IL-10被激活,并且对与TGF-β相关的IL-5表达增加具有抑制作用。