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，CMV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。用0.2LD_<50>（50%致死量）的鼠巨细胞病毒（MCMV）腹腔注射成年BALB/c小鼠4周后，在唾液腺中仍能检测到MCMV，而在肺和其它器官中则检测不到。当这些小鼠的T细胞通过单次注射抗CD 3单克隆抗体（mAb）在体内活化时，在无病毒的肺中诱导间质性肺炎。本研究利用CMV肺炎动物模型，观察了以下几个方面的变化.在持续感染MCMV的这种小鼠的肺中，在注射mAb后过量产生细胞因子如IL-2、IL-6、TNF-α和IFN-γ。然后，肺内过量产生的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水平也显著升高.一氧化氮拮抗剂的管理减轻了间质性肺炎引起的抗CD 3单抗。基于这些研究结果，我们得出结论，MCMV相关的肺炎是由苦参碱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.