Ben-Nathan D, Lustig S, Kobiler D, Danenberg H D, Lupu E, Feuerstein G
Department of Virology, Israel Institute for Biological Research, Ness-Ziona.
J Med Virol. 1992 Nov;38(3):159-66. doi: 10.1002/jmv.1890380302.
The protective effect of pretreatment with dehydroepiandrosterone (DHEA) on stress-enhanced viral encephalitis was studied in mice exposed to cold following inoculation with West Nile virus (WNV). Exposure of WNV-inoculated mice to cold water (1 +/- 0.5 degrees C, 5 minutes/day for 8 days) resulted in a mortality rate of 83% as compared to 50% in nonstressed mice (p < 0.05). The effect of cold stress was more pronounced when mice were inoculated with WN-25, a noninvasive neurovirulent variant of WNV. Mice infected with WN-25 showed no mortality, whereas cold stressed mice inoculated with the same virus had a mortality rate of 67% (p < 0.05). The administration of DHEA (serial injections of 10-20 mg/kg with or without a loading dose of 1 gm/kg) resulted in a significant reduction in the mortality rate of stressed mice inoculated with either virus (p < 0.05). Virus levels in the blood and brain of the DHEA-treated mice, were significantly lower than in the control groups. DHEA also prevented the involution of lymphoid organs in stressed mice. The present study provides direct evidence of the protective effects of DHEA as an "anti-stress" agent. Its ability to prevent mortality associated with WNV or WN-25, and involution of lymphoid organs caused by stress-induced immunosuppression, supports the notion that its activity is based on the modulation of the host response.
在接种西尼罗河病毒（WNV）后暴露于寒冷环境的小鼠中，研究了脱氢表雄酮（DHEA）预处理对压力增强型病毒性脑炎的保护作用。与未受应激的小鼠相比，将接种WNV的小鼠暴露于冷水（1±0.5摄氏度，每天5分钟，共8天）中导致死亡率为83%，而未受应激的小鼠死亡率为50%（p<0.05）。当用WN-25（WNV的一种非侵袭性神经毒性变体）接种小鼠时，冷应激的影响更为明显。感染WN-25的小鼠没有死亡，而接种相同病毒的冷应激小鼠死亡率为67%（p<0.05）。给予DHEA（连续注射10-20mg/kg，有无1g/kg的负荷剂量）可显著降低接种任一病毒的应激小鼠的死亡率（p<0.05）。DHEA处理小鼠的血液和脑中的病毒水平显著低于对照组。DHEA还可防止应激小鼠淋巴器官的退化。本研究提供了DHEA作为“抗应激”剂具有保护作用的直接证据。其预防与WNV或WN-25相关的死亡以及由应激诱导的免疫抑制引起的淋巴器官退化的能力，支持了其活性基于宿主反应调节的观点。
