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

IL-18最初被认为是诱导Th1相关细胞因子。一般来说，有利于干扰素-γ产生的因素被认为可以消除过敏性疾病。因此，我们测试了IL-18在调节哮喘中的作用。为了避免宿主来源的T细胞的背景反应，我们给非致敏小鼠注射了记忆型Th1或Th2细胞，并检测了它们在诱导哮喘中的相关作用。在接受记忆Th2细胞的小鼠中，给予Ag诱导了呼吸道炎症和气道高反应性(AHR)。相反，在接受记忆Th1细胞的小鼠中，同样的治疗只引起了呼吸道炎症，而不是AHR。然而，当这些小鼠与IL-18联合给药时，它们出现了惊人的AHR。此外，接受了从极化的Th1细胞中分离出来的表达干扰素-γ的Th1细胞的小鼠，在鼻内注射抗原和IL-18后，出现了严重的呼吸道炎症和急性呼吸道反应。因此，当Th1细胞受到抗原和IL-18的刺激时，它们会成为非常有害的细胞。新极化的Th1细胞和表达干扰素-γ的Th1细胞都强烈表达IL-18Rα链，在体外经抗原、IL-2和IL-18刺激后产生干扰素-γ、IL-9、IL-13、GM-α、肿瘤坏死因子-α、RANTES和MIP-1。因此，抗原和IL-18刺激记忆Th1细胞在幼稚宿主中诱导严重的呼吸道炎症和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.