Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.

中文翻译：

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IL-33 的中和改变了病毒性哮喘恶化的 2 型和 3 型炎症特征

呼吸道病毒感染是哮喘患者需要急诊和住院治疗的主要原因之一，气道分泌的细胞因子会在病毒感染后数小时内释放以引发这些恶化。具体而言，IL-33 通过放大 2 型炎症导致这些过敏性恶化。我们假设在 RSV 诱导的恶化中阻断 IL-33 会​​显着减少过敏性炎症。用雾化卵清蛋白 (OVA) 攻击致敏 BALB/c 小鼠以建立过敏性炎症，然后感染 RSV-A2 以产生四个治疗组：仅盐水 (Saline)、仅感染 RSV (RSV)、仅 OVA (OVA)、和用 RSV 感染 (OVA-RSV) 治疗的 OVA。肺部结果包括过敏性炎症的肺部 mRNA 和蛋白质标志物，通过细胞离心涂片和流式细胞术进行粘液细胞化生和肺免疫细胞流入的组织学。虽然在 OVA-RSV 小鼠中 RSV 感染后 6 小时检测到胸腺基质淋巴细胞生成素 (TSLP) 和 IL-33，但仅在 RSV 感染的小鼠中，IL-23 蛋白被独特地上调。OVA-RSV 动物与 RSV 或 OVA 处理的小鼠不同，因为它们的肺嗜酸性粒细胞、嗜中性粒细胞、第 2 组先天淋巴细胞 (ILC2) 和第 3 组先天淋巴细胞 (ILC3) 早在 RSV 感染后 6 小时即可检测到。中和的 IL-33 显着降低了 OVA-RSV 小鼠中的 ILC2 和嗜酸性粒细胞以及原型过敏蛋白 IL-5、IL-13、CCL17 和 CCL22。在 RSV 和 OVA-RSV 治疗的动物中，中性粒细胞和 ILC3 的数量也因抗 IL-33 治疗而减少。综合起来，