Pathogenesis and treatment of cytomegalovirus infection after organ transplantation

巨细胞病毒（CMV）引起各种类型的疾病，如视网膜炎、肝炎、肺炎、胃炎和结肠炎。其中，巨细胞病毒相关性肺炎是器官移植受者的主要并发症，其发病机制和治疗方法尚不清楚。这项研究就是为了解决这个问题而组织起来的。在成年BALB/c小鼠腹腔注射0.2 LD_<50>（50%致死剂量）的小鼠巨细胞病毒（MCMV） 4周后，在唾液腺中仍可检测到MCMV，但在肺部和其他器官中未检测到MCMV。当这些小鼠的T细胞在体内被单次注射抗cd3单克隆抗体（mAb）激活时，因此在没有病毒的肺中诱导间质性肺炎。在cmv肺炎动物模型中，我们观察到：在持续感染MCMV的小鼠肺中，注射mAb.2后，IL-2、IL-6、tnf - α和ifn - γ等细胞因子过量产生。然后，在肺中过量产生tnf - α和ifn - γ等细胞因子诱导诱导型一氧化氮合成酶（iNOS）。血清中一氧化氮的代谢产物硝酸盐和亚硝酸盐的水平也显著升高。一氧化氮拮抗剂的使用减轻了抗cd3单抗引起的间质性肺炎。基于这些发现，我们得出结论，mcmv相关肺炎是由细胞因子诱导的一氧化氮介导的。

Cytomegalovirus (CMV) causes various types of diseases such as retinitis, hepatitis, pneumonitis, gastritis and colitis. Among them, CMV-associated pneumonitis is a major complication in organ transplant recipients, as the pathogenesis and therapy for the disease is still unclear. This research was organized to solve this problem.Four weeks after intraperitoneal inoculating of 0.2 LD_<50> (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody (mAb), interstitial pneumonitis was thus induced in the lungs that were free of the virus. Using this animal model of CMV-pneumonitis, we observed the followings.1. In the lungs of such mice persistently infected with MCMV,the cytokines such as IL-2, IL-6, TNF-alpha and IFN-gamma were excessively produced after the injection of mAb.2. Then, Cytokines as TNF-alpha and IFN-gamma produced excessively in the lungs induced inducible nitric oxide synthetase (iNOS).3. A significant elevation of the serum levels of nitrate and nitrite, which are the metabolic products of nitric oxide in the serum, was also observed.4. The administration of a nitric oxide antagonist alleviated the interstitial pneumonitis provoked by anti-CD3 mAb.Based on these findings, we concluded that MCMV-associated pneumonitis is mediated by cytokine-induced nitric oxide.