Wilson E J, Medearis D N, Hansen L A, Rubin R H
Children's Service, Massachusetts General Hospital, Boston.
Antimicrob Agents Chemother. 1987 Jul;31(7):1017-20. doi: 10.1128/AAC.31.7.1017.
Immunosuppressed (from treatment with cortisone acetate and anti-thymocyte globulin) and control adult female BALB/c mice, latently infected with murine cytomegalovirus (MCMV) or lethally challenged (10(6) PFU) with MCMV intraperitoneally, were treated with 9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) intraperitoneally. A dose of 3 mg/kg reduced mortality by 50% in lethally challenged normal mice; 10 mg/kg was required in immunosuppressed mice. When 15 mg/kg was given, the onset of treatment could be delayed for 64 h after lethal challenge. DHPG did not prevent the establishment of latent MCMV infection or immunosuppression-induced reactivation. The antibody titer to MCMV in DHPG-treated mice which survived lethal challenge was 41 (reciprocal of geometric mean) 4 to 5 weeks after inoculation; such mice survived a second lethal challenge. When antiserum treatment was begun 64 h and DHPG was begun 72 h after a lethal challenge, most mice survived; most did not when either treatment alone was begun at those times. In summary, DHPG effectively treated lethal MCMV infection even in immunosuppressed mice and even when treatment onset was delayed for 64 h. Treatment did not alter the establishment or reactivation of latent infections or the induction of effective immunity. The administration of DHPG coupled with antiserum treatment may be even more effective than the administration of either alone.
用醋酸可的松和抗胸腺细胞球蛋白进行免疫抑制处理的成年雌性BALB/c小鼠以及作为对照的成年雌性BALB/c小鼠,分别处于潜伏感染鼠巨细胞病毒(MCMV)状态或经腹腔给予致死剂量(10⁶ PFU)的MCMV进行攻击,然后经腹腔给予9-(1-3-二羟基-2-丙氧基甲基)鸟嘌呤(DHPG)。3mg/kg的剂量可使经致死攻击的正常小鼠死亡率降低50%;免疫抑制小鼠则需要10mg/kg。给予15mg/kg时,致死攻击后治疗开始时间可延迟64小时。DHPG不能预防潜伏性MCMV感染的建立或免疫抑制诱导的病毒再激活。在经致死攻击后存活的用DHPG处理的小鼠中,接种后4至5周时针对MCMV的抗体滴度为41(几何平均数的倒数);此类小鼠在第二次致死攻击中存活。当在致死攻击后64小时开始抗血清治疗且72小时开始DHPG治疗时,大多数小鼠存活;而在这些时间单独开始任何一种治疗时,大多数小鼠不能存活。总之,即使在免疫抑制小鼠中,甚至在治疗开始延迟64小时的情况下,DHPG仍能有效治疗致死性MCMV感染。治疗并未改变潜伏感染的建立或再激活,也未改变有效免疫的诱导。联合给予DHPG和抗血清治疗可能比单独给予任何一种治疗更有效。