鼻腔吸入γ干扰素对大鼠变应性鼻炎的治疗作用

目的 探讨鼻腔吸入γ干扰素(interferon gamma,IFN-γ)对大鼠变应性鼻炎(allergic rhinitis,AR)的治疗作用及可能机制.方法 采用卵白蛋白、氢氧化铝建立大鼠AR模型,分为阳性对照组(B组)、IFN-γ组(c组)和丙酸倍氯米松组(D组),每组8只大鼠,分别于模型建立后第31～38天,每只每日每侧鼻腔滴入磷酸盐缓冲液50μl、IFN-γ1 μg和丙酸倍氯米松3.5 μg,另设阴性对照组(A组)大鼠8只.第39天取鼻腔灌洗液测定细胞成分、白细胞介素4和白细胞介素5浓度;取血测定血浆IgE水平;黏膜切片观察鼻腔组织病理学改变及GATA-3的表达.结果 C组鼻腔灌洗液中的嗜酸粒细胞数量(-x±s,下同)为(O.005±0.003)×104/ml,明显低于B组(0.225±0.060)x104/ml(P<0.01);C组鼻腔灌洗液中的白细胞介素4为(7.8±3.5)pg/ml,白细胞介素5为(12.5±4.3)pg/ml,均低于B组(P值均<0.01);C组血浆中总IgE为(38.5±9.6)μg/ml,卵白蛋白特异性IgE为(19.8±5.4)IU/ml,均低于B组(P值均<0.01).B组大鼠鼻腔黏膜充血、水肿,黏膜层增厚,并有嗜酸细胞为主的炎性细胞浸润,而c组大鼠上述炎性症状改变减轻.免疫组化显示B组鼻腔组织中GATA-3表达增加,而C组的表达减少.结论 鼻腔吸入IFN-γ可以抑制AR大鼠白细胞介素4和白细胞介素5的合成,抑制嗜酸粒细胞在鼻腔内的炎性浸润,降低血浆中总IgE和卵白蛋白特异性IgE水平,其机制可能与阻断GATA-3表达,从而继发抑制Th2型反应有关.

Treatment of allergic rhinitis rats by intranasal interferon gamma

OBJECTIVE: To investigate the effects and mechanism of intranasal interferon gamma (IFN-gamma) in the treatment of allergic rhinitis. METHODS: Ovalbumin (OVA) absorbed to aluminum hydroxide was used to construct the allergic rhinitis model (group C), and the normal control group (group A), the allergic rhinitis model group (group B) and beclomethasone dipropionate group (group D) consisted of 8 rats for each. PBS 50 microl was absorbed to group B, IFN-gamma 1 microg was absorbed to group C and beclomethasone dipropionate 3.5 microg was absorbed to group D on day 31 to day 38 once daily once nasal cavity. The nasal lavage fluid was collected on day 39, and the cellular constituents, levels of interleukin-4 (IL-4), interleukin-5 (IL-5) and IgE were determined, together with the pathologic changes and expression of GATA-3 were observed. RESULTS: Decrease of eosinophils [(0.005 +/- 0.003) x 10(4)/ml, x +/- s] was seen in nasal lavage fluid of group C as comparing with group B [(0.225 +/- 0.060) x 10(4)/ml, (P < 0.01)], and the levels of IL-4 (7.8 +/- 3.5) pg/ml and IL-5 (12.5 +/- 4.3) pg/ml decreased significantly in comparing with group B (P < 0.01). The serum levels of total IgE (38.5 +/- 9.6) microg/ml and ovalbumin-specific IgE (19.8 +/- 5.4) IU/ml decreased significantly in comparing with those of group B (P < 0.01). In group B, mucosal congestion and edema thickening with inflammatory cells infiltration mainly of eosinophils; in group C, the above mentioned changes were much more ameliorated. Immunohistochemistry showed significant increase of GATA-3 expression in the nosal tissue of group B but much lesser than that in group C. CONCLUSIONS: IFN-gamma can inhibit the composition of IL-4 and IL-5, and inhibit the airway inflammation with eosinophilic infiltration and the serum levels of total IgE and ovalbumin specific IgE, probably through the mechanism of restraining the Th2 reaction by blockade of GATA-3 expression in the nasal tissue.