口服低剂量细胞因子治疗过敏性哮喘
2009/07/09
许多炎症性疾病的主要特征是体内淋巴细胞亚群失衡，特别是Th1和 Th2细胞以及近期发现的Th17细胞。Th1/Th2失衡与诸多因素有关，但可以肯定的是，细胞因子在其中发挥了重要作用。在与Th2相关的疾病中，IL-4表达显著增加，而Th1相关疾病中IFN-γ和IL-12表达增加。目前对于许多炎症性疾病，虽然治疗意见中都提到以重新恢复Th1/Th2平衡为治疗目标，但作为生物活性分子，细胞因子要作为药物进行临床应用，尚存在着诸多限制，其中就包括其副作用。
本实验在小鼠过敏性哮喘模型中研究低剂量细胞因子溶液对哮喘的治疗作用。
结果显示，口服低剂量、机械性活化的IL-12和IFN-γ能缓解哮喘小鼠的支气管高反应性，恢复正常细胞因子水平。上述治疗作用同时在肺的组织学分析和支气管肺泡灌洗液细胞计数中得到证实。此外，治疗后血清中卵清蛋白特异性IgE也显著下降。本实验为与Th1/Th2失衡相关的疾病找到了一个新的治疗方法。
（林江涛 审校）
Pulm Pharmacol Ther. 2009 May 20. [Epub ahead of print]
Low dose oral administration of cytokines for treatment of allergic asthma.
Gariboldi S, Palazzo M, Zanobbio L, Dusio GF, Mauro V, Solimene U, Cardani D, Mantovani M, Rumio C; S.G.M.P. contributed equally to this work.
iMIL- italian Mucosal Immunity Laboratory, Department of Human Morphology and Biomedical Sciences "Città Studi", Università degli Studi di Milano, via Mangiagalli, 31 - 20133 Milano, Italy.
Many inflammatory diseases are characterized by an imbalance among lymphocyte populations, in particular Th1, Th2 and the recently described Th17 cells. The Th1/Th2 imbalance is linked to many factors, but certainly the role of cytokines is essential. In Th2 diseases IL-4 expression is predominant, while Th1 pathologies are characterized by high expression of IFN-gamma and IL-12. Though today the therapeutical proposal for many inflammatory diseases aims to re-establish normal levels of Th1/Th2 cytokines, the pharmacological use of cytokines, which are very active molecules, is limited by the possible collateral effects. Therefore, our study aims to determine, in a murine model of allergic asthma, the possible therapeutic activity of low dose cytokines solutions, mechanically activated. We found that oral administration of low doses IL-12 plus IFN-gamma is able to solve the bronchial hyperresponsiveness condition of mice, establishing normal cytokine levels. The anti-asthma activity was confirmed by histological analysis of lungs and bronchoalveolar lavage fluid cell count. Serum ovalbumin-specific IgE was also significantly inhibited by treatment with low-dose activated cytokines solution. These findings may suggest a novel approach to diseases which involve a Th1/Th2 imbalance.
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哮喘治疗中的免疫调节剂
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