Ayoub M, Lallouette P, Sütterlin B W, Bessler W G, Huber M, Mittenbühler K
Institut für Molekulare Medizin und Zellforschung, AG Tumorimmunologie/Vakzine, Universitätsklinikum Freiburg, Stefan-Meier-Str 8, D-79104 Freiburg, Germany.
Int Immunopharmacol. 2003 Apr;3(4):523-39. doi: 10.1016/S1567-5769(03)00031-6.
Vaccination with the antiallergic drug Histaglobin is used to treat a broad range of human allergic diseases including bronchial asthma, allergic rhinitis, and atopic dermatitis. In order to further elucidate its functional activity, Histaglobin was investigated in an in vivo mouse allergy model. Mice were sensitized with ovalbumin either prior to or after Histaglobin treatment, and its antiallergic potential was evaluated. Ovalbumin-sensitized mice exhibited increased serum levels of IL-4, tumor necrosis factor alpha (TNF-alpha), and an increase of total and ovalbumin-specific IgE; total and ovalbumin-specific IgG levels were also elevated. Subsequent administration (therapeutic treatment) of Histaglobin resulted in a decrease of total and specific serum IgE levels; total and specific IgG1 serum levels were reduced by more than 50% and 45%, respectively; the mice displayed a down-regulation of IL-4 and TNF-alpha serum levels and showed increased levels of IFN-gamma and IgG2a. Mice pretreated with Histaglobin, prior to ovalbumin sensitization (prophylactic treatment), were found to be widely unresponsive to ovalbumin. They exhibited higher serum levels of IFN-gamma and IgG2a (total and specific) compared to saline-treated control mice. The inhibitory effects were still observed 1 month post-immunization. Our data, indicating a Histaglobin-induced modulation of the Th1/Th2 balance in favour of Th1, correspond with the well-known antiallergic activity of Histaglobin observed in patients.
使用抗组胺药物组胺球蛋白进行疫苗接种可用于治疗多种人类过敏性疾病，包括支气管哮喘、过敏性鼻炎和特应性皮炎。为了进一步阐明其功能活性，在体内小鼠过敏模型中对组胺球蛋白进行了研究。在组胺球蛋白治疗之前或之后用卵清蛋白使小鼠致敏，并评估其抗过敏潜力。卵清蛋白致敏的小鼠血清白细胞介素-4（IL-4）、肿瘤坏死因子α（TNF-α）水平升高，总IgE和卵清蛋白特异性IgE增加；总IgG和卵清蛋白特异性IgG水平也升高。随后给予组胺球蛋白（治疗性治疗）导致总血清IgE和特异性血清IgE水平降低；总血清IgG1和特异性血清IgG1水平分别降低超过50%和45%；小鼠IL-4和TNF-α血清水平下调，干扰素-γ（IFN-γ）和IgG2a水平升高。在卵清蛋白致敏之前用组胺球蛋白预处理的小鼠（预防性治疗）被发现对卵清蛋白广泛无反应。与盐水处理的对照小鼠相比，它们表现出更高的IFN-γ和IgG2a（总水平和特异性水平）血清水平。在免疫后1个月仍观察到抑制作用。我们的数据表明组胺球蛋白诱导Th1/Th2平衡向Th1方向调节，这与在患者中观察到的组胺球蛋白众所周知的抗过敏活性一致。
