Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
Int Arch Allergy Immunol. 2010;152(4):303-12. doi: 10.1159/000288283. Epub 2010 Feb 26.
Using a T helper (Th)1/Th2 disease model, we previously showed that genetically determined Th development depends on dendritic cell-derived interleukin (IL)-1alpha. In Leishmania major infections, Th1 immunity develops if IL-1alpha is present during T cell priming, whereas at later time points, IL-1alpha worsens disease outcome. In the present study, we determined the role of IL-1alpha in other Th2-mediated diseases.
BALB/c mice were subjected to delayed-type hypersensitivity (DTH) or ovalbumin (OVA)/alum-induced allergic asthma in the presence or absence of IL-1alpha.
In DTH, mice treated with IL-1alpha during sensitization with keyhole limpet hemocyanin (KLH)/alum developed decreased footpad swelling associated with elevated KLH-specific interferon-gamma levels. In asthma, significantly decreased airway hypersensitivity responses (AHRs) were detected upon treatment with IL-1alpha during T cell priming. In contrast to control mice, IL-1alpha-treated mice showed reduced peribronchial inflammatory infiltrates. The bronchoalveolar lavage (BAL) fluid contained significantly decreased eosinophil numbers (approximately 50%), but 4 times more neutrophils. The BAL fluid of IL-1alpha-treated BALB/c exhibited reduced amounts of IL-5 and OVA-specific IgE serum levels. In contrast, IL-1alpha treatment at later time points after sensitization or during allergen challenge worsened AHR, had no effect on lung inflammation and BAL fluid cell composition. Furthermore, cytokine levels (IL-5, IL-13) and antigen-specific IgE were increased or unaltered under these conditions.
Similarly to leishmaniasis, IL-1alpha administration during sensitization of Th2-mediated allergic reactions suppresses the course of disease by shifting the immune response towards Th1, whereas later treatments worsen disease outcome. Future studies will elucidate the therapeutic value of IL-1alpha in asthmatic patients.
使用辅助性 T 细胞（Th）1/Th2 疾病模型，我们之前表明，树突状细胞衍生的白细胞介素（IL）-1α决定了 Th 细胞的发育。在大孢子虫感染中，如果在 T 细胞初始阶段存在 IL-1α，则会产生 Th1 免疫，而在稍后的时间点，IL-1α会加重疾病的结果。在本研究中，我们确定了 IL-1α在其他 Th2 介导疾病中的作用。
BALB/c 小鼠在存在或不存在 IL-1α的情况下，进行迟发型超敏反应（DTH）或卵清蛋白（OVA）/明矾诱导的过敏性哮喘。
在 DTH 中，用钥孔血蓝蛋白（KLH）/明矾进行致敏时，用 IL-1α处理的小鼠出现足垫肿胀减轻，与 KLH 特异性干扰素-γ水平升高相关。在哮喘中，在 T 细胞初始阶段用 IL-1α治疗时，检测到气道高反应性（AHR）显著降低。与对照小鼠相比，用 IL-1α处理的小鼠显示出支气管周围炎症浸润减少。支气管肺泡灌洗液（BAL）中的嗜酸性粒细胞数量明显减少（约 50%），但中性粒细胞增加了 4 倍。用 IL-1α处理的 BALB/c 的 BAL 液中含有较少的 IL-5 和 OVA 特异性 IgE 血清水平。相比之下，在致敏后或在过敏原攻击时的后期用 IL-1α治疗会加重 AHR，对肺炎症和 BAL 液细胞组成没有影响。此外，在这些条件下，细胞因子水平（IL-5、IL-13）和抗原特异性 IgE 增加或未改变。
与利什曼病类似，在 Th2 介导的过敏反应的致敏期间给予 IL-1α通过将免疫反应转向 Th1 来抑制疾病的进程，而后期治疗会加重疾病的结果。未来的研究将阐明 IL-1α在哮喘患者中的治疗价值。
