Savolainen J, Nieminen K, Laaksonen K, Laiho T, Jacobsen L, Lahesmaa R, Terho E O, Valovirta E
Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland.
Allergy. 2007 Aug;62(8):949-53. doi: 10.1111/j.1398-9995.2007.01426.x.
Signalling lymphocytic activation molecule (SLAM) and interleukin (IL)-18 induce interferon (IFN)-gamma production from Th1 cells. The allergen-induced SLAM and IL-18 mRNA expressions are increased during subcutaneous immunotherapy (SCIT), but nothing is known about their role during sublingual immunotherapy (SLIT). Transcription factor GATA-3 is associated with Th2 cells but its role in SCIT and SLIT is yet unexplored. This study was undertaken to analyse the allergen induced in vitro mRNA expression of IL-18, SLAM and GATA-3 in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR) during SLIT.
Ten patients with AR undergoing pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with 24,000 SQ-U of mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included. Peripheral blood mononuclear cell were stimulated with birch extract prior to, after 1 and 2 years of the treatment. The mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan); Applied Biosystems, Foster City, CA, USA).
The expression of IL-18 mRNA was increased in the high-dose group in comparison to the placebo group after 1 year of therapy (P = 0.028) and had an inverse correlation with the late phase skin reaction after the second study year (r = -0.41, P = 0.041). SLAM mRNA expression increased in the high-dose group from baseline to 1 year (P = 0.028) and correlated with IL-10 (r = 0.96, P < 0.0001) and transforming growth factor-beta (r = 0.80, P = 0.0037) mRNA expression. No significant changes were seen in GATA-3 mRNA expression.
During SLIT, IL-18 and SLAM are upregulated, suggesting that the Th2 type inflammatory response is downregulated during SLIT by increased Th1 type response.
信号淋巴细胞激活分子（SLAM）和白细胞介素（IL）-18可诱导Th1细胞产生干扰素（IFN）-γ。在皮下免疫治疗（SCIT）期间，变应原诱导的SLAM和IL-18 mRNA表达增加，但关于它们在舌下免疫治疗（SLIT）中的作用尚无相关研究。转录因子GATA-3与Th2细胞相关，但其在SCIT和SLIT中的作用尚未得到探索。本研究旨在分析变应原诱导的变应性鼻炎（AR）儿童在SLIT期间外周血单个核细胞（PBMC）中IL-18、SLAM和GATA-3的体外mRNA表达情况。
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、榛子和桤木混合物24,000 SQ-U治疗的患者，以及10例接受安慰剂治疗的患者。在治疗前、治疗1年和2年后，用桦树提取物刺激外周血单个核细胞。使用实时荧光定量逆转录聚合酶链反应（TaqMan）（美国加利福尼亚州福斯特城应用生物系统公司）评估mRNA表达。
治疗1年后，高剂量组IL-18 mRNA表达相较于安慰剂组增加（P = 0.028），且与研究第二年的迟发性皮肤反应呈负相关（r = -0.41，P = 0.041）。高剂量组SLAM mRNA表达从基线到1年增加（P = 0.028），并与IL-10（r = 0.96，P < 0.0001）和转化生长因子-β（r = 0.80，P = 0.0037）mRNA表达相关。GATA-3 mRNA表达未见明显变化。
在SLIT期间，IL-18和SLAM上调，提示SLIT期间Th2型炎症反应通过增强Th1型反应而下调。
