IL-33在呼吸道合胞病毒(RSV)感染致哮喘急性发作中的作用

 目的 研究IL-33在呼吸道合胞病毒（respiratory syncytial virus，RSV）感染致哮喘急性发作中的作用。方法 将24只3周龄SPF级BALB/c雌性小鼠随机分为PBS组、RSV组、卵清白蛋白（ovalbumin，OVA）组和OVA/RSV组，每组6只。首先应用OVA或PBS激发并致敏小鼠，再感染RSV致哮喘急性发作。麻醉后处死小鼠。ELISA法测小鼠血清总IgE水平、支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）及肺组织IL-33蛋白水平；瑞氏/吉姆萨染色后测BALF细胞总数及各细胞分类计数；取肺组织病理切片HE染色；real-time PCR测T辅助细胞2型（T helper 2，Th2）细胞因子、IL-33等mRNA表达。结果 OVA组与PBS组相比，血清IgE水平明显升高（P<0.05）。OVA/RSV组中BALF细胞总数较OVA组显著增加，主要表现为巨噬细胞和中性粒细胞的增加。病理切片HE染色可见OVA/RSV组小气道周围炎性细胞浸润更加明显。以上表明RSV感染OVA诱导哮喘急性发作的小鼠模型成功建立。real-time PCR显示：与OVA组相比，OVA/RSV组IL-13以及IL-33 mRNA表达显著增加（P<0.05），IL-5和ST2表达有所增加，但差异无统计学意义。ELISA结果显示：与OVA组相比，OVA/RSV组肺组织中IL-33浓度增高更加显著（P<0.05），BALF中IL-33浓度也有所增加，但差异无统计学意义。结论 IL-33可能通过启动Th2型免疫反应在RSV感染诱导哮喘急性发作小鼠模型中起重要作用。

The role of IL-33 in the pathogenesis of respiratory syncytial virus (RSV) infection-induced acute exacerbation of asthma

Objective To explore the role of IL-33 in the pathogenesis of respiratory syncytial virus (RSV) infection-induced acute exacerbation of asthma. Methods Twenty-four female BALB/c mice at 3-week-old were randomly divided into PBS group,RSV group,ovalbumin (OVA) group and OVA/RSV group.All mice were housed under SPF conditions.First,the mice were treated with OVA or PBS to establish asthma model.Then,RSV infected the mice for acute asthma exacerbation.Finally,the mice were sacrificed under anesthesia and the total IgE protein in serum was measured by ELISA.The total cell counts and differential cells in bronchoalveolar lavage fluid (BALF) were counted after Wright-Giemsa staining.Lung pathology was determined by HE staining.The gene expressions of IL-33 and Th2 cytokines were measured by real-time PCR.IL-33 protein in the lung or BALF was detected by ELISA. Results Compared with PBS group,the total IgE level in serum was significantly elevated in OVA group.Compared with OVA group,the total cells number in BALF of OVA/RSV group was increased significantly,mainly for macrophages and neutrophils.The inflammatory cells infiltration around the small airway in OVA/RSV group was more obvious than other groups.Those did confirm that the mouse model of RSV acute infection of OVA-induced asthma was established well.RSV acute infection in OVA-treated mice could stimulate the further increased expressions of IL-13 and IL-33 mRNA,but the expressions of IL-5 and ST2 mRNA did not change significantly. In terms of protein level detected by ELISA,compared with OVA group,RSV acute infection couldelevate the level of IL-33 protein in the lung homogenate,but there was no significant difference in BALF. Conclusions IL-33 may play an important role in the RSV acute infection of OVA-induced asthma mice by initiating the Th2 immune response.