Stals F S, Wagenaar S S, Bruggeman C A
Department of Medical Microbiology, University of Limburg, Maastricht, The Netherlands.
Antiviral Res. 1994 Oct;25(2):147-60. doi: 10.1016/0166-3542(94)90103-1.
The combined effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and hyper immune serum (HIS) was studied in two different rat models. In the first model, a lethal generalized rat cytomegalovirus (RCMV) infection was established in immunosuppressed Brown Norway (BN) rats. Treatment with DHPG or hyper immune serum (HIS) effectively reduced both mortality rate and virus titers in the liver and lungs. By combined treatment the effective dose of both DHPG and HIS was reduced to 25%. The fractionary effective dose was 0.5, indicating a moderate synergistic effect on survival. Combined treatment also established a significant reduction of virus titers in lungs and liver (P < 0.01), but not in spleen. In the second model, interstitial pneumonia (IP) was established in RCMV-infected immunosuppressed BN rats after allogeneic bone marrow transplantation. IP was characterized by infiltration of mononuclear cells and diffuse thickening of the alveolar septal wall. DHPG reduced virus titers in the lungs but had no effect on IP. In contrast, HIS significantly reduced both virus titers and histopathologic changes in the lungs. Combined DHPG and HIS treatment minimized virus titers in internal organs and CMV-induced IP. Likewise, combined DHPG and control immune serum treatment significantly reduced immunopathologic changes in the lungs.
在两种不同的大鼠模型中研究了9-(1,3-二羟基-2-丙氧甲基)鸟嘌呤（DHPG，更昔洛韦）与超免疫血清（HIS）的联合作用。在第一个模型中，在免疫抑制的棕色挪威（BN）大鼠中建立了致死性全身性大鼠巨细胞病毒（RCMV）感染。用DHPG或超免疫血清（HIS）治疗可有效降低死亡率以及肝脏和肺中的病毒滴度。通过联合治疗，DHPG和HIS的有效剂量均降低至25%。分级有效剂量为0.5，表明对生存有中度协同作用。联合治疗还使肺和肝脏中的病毒滴度显著降低（P < 0.01），但脾脏中未降低。在第二个模型中，在同种异体骨髓移植后，在RCMV感染的免疫抑制BN大鼠中建立了间质性肺炎（IP）。IP的特征是单核细胞浸润和肺泡间隔壁弥漫性增厚。DHPG降低了肺中的病毒滴度，但对IP没有影响。相比之下，HIS显著降低了肺中的病毒滴度和组织病理学变化。DHPG和HIS联合治疗使内脏器官中的病毒滴度和CMV诱导的IP降至最低。同样，DHPG和对照免疫血清联合治疗显著降低了肺中的免疫病理变化。
