Selgrade M J, Daniels M J, Burleson G R, Lauer L D, Dean J H
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Int J Immunopharmacol. 1988;10(7):811-8. doi: 10.1016/0192-0561(88)90004-5.
Susceptibility to murine cytomegalovirus (MCMV) was enhanced by treating B6C3F1 and CD-1 mice subcutaneously with 100 mg 7,12-dimethyl-benz[a]anthracene (DMBA)/kg fractionated over a 2 week period prior to sub-lethal infection. Virus-augmented natural killer cell (NKC) activity was depressed in B6C3F1 mice treated with 100 mg DMBA/kg, while serum interferon (IFN) levels were unaffected. Treatment with 50 mg DMBA/kg had no effect on susceptibility to virus or virus-augmented NKC activity. Susceptibility to MCMV was not affected by treating mice with 400 mg benzo[a]pyrene (B[a]P)/kg using the same exposure regimen. Virus-augmented NKC activity was suppressed in B[a]P-treated mice, but the magnitude of the suppression (18%) was much less than that for DMBA-treated mice (39%). Susceptibility to MCMV, virus-augmented NKC and IFN induction were not affected in mice treated intraperitoneally with 50 mg cyclosporin A (CSA)/kg/day for 5 days and infected on the 5th day of treatment. In contrast, enhanced susceptibility to MCMV and depressed NKC activity were observed in mice treated by the same exposure regimen on days 1-5 post infection. Susceptibility was not affected by CSA given on days 5-9 post infection. The data are useful not only because they show that DMBA and appropriately-timed CSA treatments suppress virus augmented NKC and enhance susceptibility to MCMV, but also because they help to define the relative importance of certain immune responses in defending against the infection, thus improving the usefulness of MCMV as a host resistance model for immunotoxicity testing. The data suggest that chemicals which depress NKC are likely to enhance susceptibility to MCMV, and conversely that effects on NKC should be suspected when chemical exposure enhances susceptibility to MCMV.
在亚致死性感染前2周内，给B6C3F1和CD-1小鼠皮下分次注射100 mg 7,12-二甲基苯并[a]蒽（DMBA）/kg，可增强其对鼠巨细胞病毒（MCMV）的易感性。用100 mg DMBA/kg处理的B6C3F1小鼠中，病毒增强的自然杀伤细胞（NKC）活性受到抑制，而血清干扰素（IFN）水平未受影响。用50 mg DMBA/kg处理对病毒易感性或病毒增强的NKC活性没有影响。使用相同的暴露方案，用400 mg苯并[a]芘（B[a]P）/kg处理小鼠，对MCMV易感性没有影响。B[a]P处理的小鼠中病毒增强的NKC活性受到抑制，但抑制程度（18%）远低于DMBA处理的小鼠（39%）。用50 mg环孢素A（CSA）/kg/天腹腔注射小鼠5天，并在处理第5天进行感染，对MCMV易感性、病毒增强的NKC和IFN诱导均无影响。相反，在感染后第1 - 5天用相同暴露方案处理的小鼠中，观察到对MCMV的易感性增强和NKC活性降低。感染后第5 - 9天给予CSA对易感性没有影响。这些数据不仅表明DMBA和适时的CSA处理可抑制病毒增强的NKC并增强对MCMV的易感性，还因为它们有助于确定某些免疫反应在抵御感染中的相对重要性，从而提高MCMV作为免疫毒性测试宿主抗性模型的实用性。数据表明，抑制NKC的化学物质可能会增强对MCMV的易感性，反之，当化学物质暴露增强对MCMV的易感性时，应怀疑其对NKC有影响。
