Analysis of IL-18-induced type-1 bronchial asthma

IL-18最初被认为是诱导Th 1相关的细胞因子。一般而言，认为有利于IFN-γ产生的因素可消除过敏性疾病。因此，我们测试了IL-18在支气管哮喘调节中的作用。为了避免宿主来源的T细胞的背景反应，我们将记忆型Th 1或Th 2细胞给予未致敏小鼠，并检查它们在诱导支气管哮喘中的相关作用。在接受记忆性Th 2细胞的小鼠中，给予Ag诱导气道炎症和气道高反应性（AHR）。相反，相同的治疗只诱导气道炎症，但没有AHR小鼠接受记忆Th 1细胞。然而，当这些小鼠与IL-18共施用时，它们发展出显著的AHR。此外，接受了从极化Th 1细胞分选的表达IFN-γ的Th 1细胞的小鼠在鼻内施用Ag和IL-18后发生了严重的气道炎症和AHR。因此，当Th 1细胞被Ag和IL-18刺激时，它们变成非常有害的细胞。新极化的Th 1细胞和表达IFN-γ的Th 1细胞均强烈表达IL-18 R α链，在体外经Ag、IL-2和IL-18刺激后产生IFN-γ、IL-9、IL-13、GM-CSF、TNF-α、RANTES和MIP-1α。因此，Ag和IL-18刺激记忆性Th 1细胞以诱导幼稚宿主中的严重气道炎症和AHR。

IL-18 was originally regarded to induce Th1-related cytokines. In general, factors favoring IFN-γ production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their relevant role in induction of bronchial asthma. Administration of Ag induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were co-administered with IL-18. Furthermore, mice having received IFN-γ-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR following intranasal administration of Ag and IL-18. Thus, Th1 cells become very harmful cells when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-γ-expressing Th1 cells, both of which express IL-18Rα chain strongly, produce IFN-γ, IL-9, IL-13, GM-CSF, TNF-α, RANTES and MIP-1α upon stimulation with Ag, IL-2 and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.