Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice

Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice
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DOI:
10.1046/j.1365-2222.2002.01389.x
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发表时间:
2002-06-01
影响因子:
6.1
通讯作者:
Nishizaki, K
Nishizaki, K
中科院分区:
医学2区
文献类型:
--
作者:
Hattori, H;Okano, M;Nishizaki, K

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背景一些流行病学和实验研究表明,暴露于病原体,如那些从属分枝杆菌导致抑制过敏性致敏和炎症。然而,病原体来源的可溶性抗原是否具有调节变应性鼻炎发病机制的潜力知之甚少。目的我们试图确定应用纯化的结核分枝杆菌蛋白衍生物(PPD)是否可以使用最近开发的海洋模型抑制变应性鼻炎的发生和/或加重。我们通过RT-PCR研究了PPD的单次鼻内应用是否可以引起鼻中细胞因子的产生。用曼氏血吸虫虫卵抗原(SEA)反复鼻内致敏BALB/c小鼠,不加佐剂。PPD在致敏前或致敏后通过不同途径应用。SEA-特异性抗体,鼻嗜酸性粒细胞和细胞因子的生产进行了比较,在小鼠之间,有或没有收到PPD treatment.Results IFN-γ,但没有IL-4,在鼻组织中检测到12至48小时后,一个单一的鼻内应用10 μ g PPD。在SEA致敏前和致敏期间反复鼻内应用PPD可显著抑制SEA特异性IgE/IgG 1和鼻嗜酸性粒细胞增多症的产生。此外,它部分抑制鼻腔淋巴细胞对SEA的反应产生IL-4。相反,这种处理导致IFN-γ产生的显著增加。从另一方面来说。在同一时期,通过脚垫施用PPD没有效果。SEA致敏后重复鼻内应用PPD对变应性炎症无加重作用。结论这些结果表明,局部应用PPD以及随后诱导IFN-γ可抑制小鼠变应性鼻炎的发生,但不会加剧。这表明病原体来源的抗原具有潜在的预防和预防变应性鼻炎的作用。
Background Several epidemiological and experimental studies have demonstrated that exposure to pathogens such as those from the genus Mycobacterium leads to the suppression of allergic sensitization and inflammation. However, little is known as to whether pathogen-derived soluble antigens have the potential to modulate the pathogenesis of allergic rhinitis.Objective We sought to deter-mine whether application of purified protein derivative (PPD) from Mycobacterium tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis using a recently developed marine model.Methods First, we investigated whether a single intranasal application of PPD could elicit cytokine production in the nose by RT-PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni egg antigen (SEA) intranasally without an adjuvant. PPD was applied through different routes either before or after sensitization. The production of SEA-specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was compared among mice that had or had not received PPD treatment.Results IFN-gamma, but not IL-4, was detected in the nasal tissue 12 to 48 h after a single intranasal application of 10 mug PPD. Repeated intranasal application of PPD prior to and during sensitization with SEA significantly inhibited the production of both SEA-specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially inhibited the production of IL-4 by nasal lymphocytes in response to SEA. Conversely, this treatment led to a significant increase in IFN-gamma production. On the other hand. PPD applied through the footpad had no effect over the same period. Repeated intranasal application of PPD after sensitization with SEA had no exacerbative effect on allergic inflammation.Conclusion These results indicate that the local application of PPD, and the subsequent induction of IFN-gamma inhibits the initiation, but not the exacerbation, of allergic rhinitis in mice, This suggests that pathogen-derived antigens have potential for use in the prevention and prophylaxis of allergic rhinitis.