Wright E D, Christodoulopoulos P, Small P, Frenkiel S, Hamid Q
Department of Otolaryngology, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Laryngoscope. 1999 Apr;109(4):551-6. doi: 10.1097/00005537-199904000-00006.
Th-2 type cytokine production (Interleukin-4 [IL-4] and interleukin-5 [IL5]) has been demonstrated to play a significant role in the pathophysiology of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has been shown to reduce the expression of Th-2 type cytokines in vivo. However, the contribution and expression of Th-2 type cytokine receptors in AR and their response to corticosteroid treatment remain to be clarified. Objectives of the current study are 1. To examine the expression of the cytokine IL-4 and IL-5 receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast this with the expression of the receptor for the Th-1 type cytokine, interferon-gamma receptor (IFN-gammaR), and 2. to examine the effects of pretreatment with topical corticosteroid before allergen challenge on the expression of these same receptors.
Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment.
Immunocytochemistry (alkaline phosphatase-antialkaline phosphatase labeling [APAAP] technique) was used to stain nasal biopsy specimens before and after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, major basic protein (MBP), IL-4R, IL-5R, and IFN-gammaR.
Following allergen challenge, we observed a significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P<.05), as well as a significant decrease in the expression of the Th-1 type cytokine receptor (IFN-gammaR; P<.05). Pretreatment with topical corticosteroids before nasal allergen challenge resulted in decreased expression of IL-4R (P<.05) and IL-5R (P<.05) and increased expression of IFN-gammaR (P<.05). Further, IL-4R and IL-5R expression correlated with eosinophil infiltration in the tissues.
We have demonstrated that in AR, cytokine receptors for IL-4, IL-5, and IFN-gamma follow a similar pattern to their ligands. In addition, pretreatment with topical corticosteroids was shown to alter the cytokine receptor expression pattern from a Th-2 profile more toward a Th-1 profile.
已证实Th2型细胞因子产生（白细胞介素4 [IL-4]和白细胞介素5 [IL-5]）在变应性鼻炎（AR）的病理生理学中起重要作用，且已表明局部用皮质类固醇治疗AR可在体内降低Th2型细胞因子的表达。然而，Th2型细胞因子受体在AR中的作用及表达情况以及它们对皮质类固醇治疗的反应仍有待阐明。本研究的目的是：1. 检测鼻过敏原激发模型中细胞因子IL-4和IL-5受体（IL-4R和IL-5R）的表达，并将其与Th1型细胞因子干扰素-γ受体（IFN-γR）的表达进行对比；2. 检测在过敏原激发前局部用皮质类固醇预处理对这些相同受体表达的影响。
随机前瞻性研究，14名豚草过敏受试者平均分为安慰剂组和皮质类固醇预处理组。
采用免疫细胞化学（碱性磷酸酶-抗碱性磷酸酶标记[APAAP]技术）对过敏原激发前后的鼻活检标本进行染色。所用抗体包括抗CD3、CD4、CD8、主要碱性蛋白（MBP）、IL-4R、IL-5R和IFN-γR。
过敏原激发后，我们观察到Th2型细胞因子受体（IL-4R和IL-5R）显著增加（P<0.05），以及Th1型细胞因子受体（IFN-γR）的表达显著降低（P<0.05）。在鼻过敏原激发前用局部皮质类固醇预处理导致IL-4R（P<0.05）和IL-5R（P<0.05）表达降低，IFN-γR表达增加（P<0.05）。此外，IL-4R和IL-5R表达与组织中的嗜酸性粒细胞浸润相关。
我们已证明，在AR中，IL-4、IL-5和IFN-γ的细胞因子受体与其配体遵循相似的模式。此外，局部用皮质类固醇预处理可使细胞因子受体表达模式从Th2型向Th1型转变。
