Kong Xiaoyuan, Hellermann Gary R, Patton Geoff, Kumar Mukesh, Behera Aruna, Randall Timothy S, Zhang Jian, Lockey Richard F, Mohapatra Shyam S
Department of Internal Medicine, Division of Allergy and Immunology, Joy McCann Culverhouse Airway Disease Research Center, University of South Florida College of Medicine, USA.
Virol J. 2005 Feb 8;2:3. doi: 10.1186/1743-422X-2-3.
Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants and children, which can be fatal, especially in immunocompromised patients. The BALB/c mouse, currently used as a model for studying RSV immunopathology, is semi-permissive to the virus. A mouse model that more closely mimics human RSV infection is needed. Since immunocompromised conditions increase risk of RSV infection, the possibility of enhancing RSV infection in the BALB/c mouse by pretreatment with cyclophosphamide was examined in this study. BALB/c mice were treated with cyclophosphamide (CYP) and five days later, they were infected with RSV intranasally. Pulmonary RSV titers, inflammation and airway hyperresponsiveness were measured five days after infection.
CYP-treated mice show higher RSV titers in their lungs of than the untreated mice. Also, a decreased percentage of macrophages and an increased number of lymphocytes and neutrophils were present in the BAL of CYP-treated mice compared to controls. The CYP-treated group also exhibited augmented bronchoalveolar and interstitial pulmonary inflammation. The increased RSV infection in CYP-treated mice was accompanied by elevated expression of IL-10, IL-12 and IFN-gamma mRNAs and proteins compared to controls. Examination of CYP-treated mice before RSV infection showed that CYP treatment significantly decreased both IFN-gamma and IL-12 expression.
These results demonstrate that CYP-treated BALB/c mice provide a better model for studying RSV immunopathology and that decreased production of IL-12 and IFN-gamma are important determinants of susceptibility to RSV infection.
呼吸道合胞病毒（RSV）感染可导致婴幼儿细支气管炎，甚至可能致命，在免疫功能低下的患者中尤其如此。目前用于研究RSV免疫病理学的BALB/c小鼠对该病毒呈半容许状态。因此需要一种更能模拟人类RSV感染的小鼠模型。由于免疫功能低下会增加RSV感染风险，本研究检测了用环磷酰胺预处理BALB/c小鼠以增强RSV感染的可能性。给BALB/c小鼠注射环磷酰胺（CYP），五天后经鼻内感染RSV。感染五天后检测肺部RSV滴度、炎症反应和气道高反应性。
经CYP处理的小鼠肺部RSV滴度高于未处理的小鼠。此外，与对照组相比，经CYP处理的小鼠支气管肺泡灌洗液中的巨噬细胞百分比降低，淋巴细胞和中性粒细胞数量增加。经CYP处理的组还表现出支气管肺泡和间质性肺部炎症加剧。与对照组相比，经CYP处理的小鼠RSV感染增加，同时IL-10、IL-12和IFN-γ的mRNA及蛋白表达升高。对RSV感染前经CYP处理的小鼠进行检测发现，CYP处理显著降低了IFN-γ和IL-12的表达。
这些结果表明，经CYP处理的BALB/c小鼠为研究RSV免疫病理学提供了更好的模型，IL-12和IFN-γ产生减少是易感染RSV的重要决定因素。
