Kirmaz Cengiz, Bayrak Papatya, Yilmaz Ozge, Yuksel Hasan
Celal Bayar University Medical Faculty, Department of Internal Medicine, Division of Immunology and Allergy, Manisa, Turkey.
Eur Cytokine Netw. 2005 Jun;16(2):128-34.
Allergic rhinitis (AR) is a disease characterized by IgE-mediated, allergic inflammation of the nasal mucosa. T helper (Th) 2 cells play an important role in the development of IgE-mediated diseases such as AR, with local overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic inflammation. Th1 cytokines (IL-12 and IFN-gamma) are known to suppress this Th2 immune response, aiding the treatment of these diseases. Beta-1,3-1,6-glucan (Glucan) is an immunomodulator stimulating particularly the antitumor response. An efficient antitumor stimulation can be achieved through a Th1-mediated immune response.
The aim of this study was to investigate the effects of Glucan on the immunopathogenic processes in the microenvironment to determine if it reverses the Th2-mediated immune response in AR to Th1-mediated response.
24 Olea europea mono-sensitized patients with AR were randomized into Glucan and placebo groups. The Glucan group consisted of 12 patients who received Glucan treatment for 12 weeks, while the placebo group of 12 patients received placebo during the same period. A nasal provocation test (NPT) with Olea europea was performed at the beginning and end of treatment, and nasal lavage followed the positive NPT. IL-4, IL-5, IFN-gamma and IL-12 levels and the eosinophil count (%) were measured in nasal lavage fluid (NLF) samples. Simultaneously, peripheral blood eosinophil % values were measured.
After treatment, IL-4 and IL-5 levels in NLF from the Glucan group were found to have decreased significantly (p = 0.027, p = 0.04; respectively), while IL-12 levels were found to have significantly increased (p = 0.008). However, IFN-gamma levels had not changed. On the other hand, none of the cytokine levels had changed significantly in the placebo group following treatment. Moreover, the percentage of eosinophils in the NLF was found to have decreased significantly after treatment in the Glucan group (p = 0.01), while that of the placebo group did not change. Peripheral blood percentage eosinophil levels had not changed significantly in any group.
Th2-originated IL-4 and IL-5 levels responsible for the allergic inflammatory response in the microenvironment of patients with AR, are decreased with Glucan while levels of Th1-originated IL-12 are increased. Moreover, eosinophils, which are important effector cells of the inflammatory response, are decreased in the microenvironment. As a result, Glucan may have a role as an adjunct to standard treatment in patients with AR.
变应性鼻炎(AR)是一种以IgE介导的鼻黏膜变应性炎症为特征的疾病。辅助性T(Th)2细胞在AR等IgE介导疾病的发生发展中起重要作用,在变应性炎症部位局部过度产生Th2细胞因子(白细胞介素-4、白细胞介素-5和白细胞介素-13)。已知Th1细胞因子(白细胞介素-12和干扰素-γ)可抑制这种Th2免疫反应,有助于这些疾病的治疗。β-1,3-1,6-葡聚糖(葡聚糖)是一种免疫调节剂,尤其能刺激抗肿瘤反应。可通过Th1介导的免疫反应实现有效的抗肿瘤刺激。
本研究旨在探讨葡聚糖对微环境中免疫病理过程的影响,以确定其是否能将AR中Th2介导的免疫反应逆转至Th1介导的反应。
24例对油橄榄单致敏的AR患者被随机分为葡聚糖组和安慰剂组。葡聚糖组由12例接受葡聚糖治疗12周的患者组成,而安慰剂组的12例患者在同一时期接受安慰剂治疗。在治疗开始和结束时进行油橄榄鼻激发试验(NPT),阳性NPT后进行鼻腔灌洗。检测鼻腔灌洗液(NLF)样本中的白细胞介素-4、白细胞介素-5、干扰素-γ和白细胞介素-12水平以及嗜酸性粒细胞计数(%)。同时,检测外周血嗜酸性粒细胞%值。
治疗后,葡聚糖组NLF中的白细胞介素-4和白细胞介素-5水平显著降低(分别为p = 0.027,p = 0.04),而白细胞介素-12水平显著升高(p = 0.008)。然而,干扰素-γ水平未改变。另一方面,安慰剂组治疗后细胞因子水平均无显著变化。此外,葡聚糖组治疗后NLF中嗜酸性粒细胞百分比显著降低(p = 0.01),而安慰剂组未改变。任何组的外周血嗜酸性粒细胞百分比水平均无显著变化。
葡聚糖可降低AR患者微环境中引起变应性炎症反应的Th2源性白细胞介素-4和白细胞介素-5水平,同时提高Th1源性白细胞介素-12水平。此外,炎症反应的重要效应细胞嗜酸性粒细胞在微环境中减少。因此,葡聚糖可能作为AR患者标准治疗的辅助药物发挥作用。