Bonilla E, Rodón C, Valero N, Pons H, Chacín-Bonilla L, Garcia Tamayo J, Rodríguez Z, Medina-Leendertz S, Añez F
Instituto de Investigaciones Clínicas, Universidad de Zulia, Maracaibo, Venezuela.
Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):207-10. doi: 10.1016/s0035-9203(01)90170-1.
Male albino mice immunodepressed after the injection of dexamethasone (DEX) were inoculated intraperitoneally with the Guajira strain of Venezuelan equine encephalomyelitis (VEE) virus. Melatonin (MLT) was administered daily, at a dose of 500 micrograms/kg bodyweight, for 3 days before virus inoculation and 10 days after. Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were determined in all the experimental groups (control, DEX, DEX + MLT, DEX + VEE, DEX + VEE + MLT, VEE and MLT). At day 6 after the virus inoculation, the survival rate was significantly increased from 0% in group DEX + VEE to 32.5% in the group of immunodepressed infected mice treated with MLT (DEX + VEE + MLT). By day 10 a survival rate of 10% was found in group DEX + VEE + MLT and 0% in group VEE. No alterations in IL-2 serum levels were observed. MLT increased GM-CSF in control and in DEX-treated mice. In the VEE virus-infected mice treated with DEX, serum levels of GM-CSF increased progressively from day 1 to 5 postinoculation. In contrast, the levels of GM-CSF in infected immunodepressed mice treated with MLT decreased significantly from day 1 to 5 postinoculation. At day 5 after viral inoculation, no differences were detected in the cerebral viral titres in groups VEE, DEX + VEE and DEX + MLT + VEE. These results show that MLT does not inhibit VEE viral replication in the brain of immunodepressed mice.
给雄性白化小鼠注射地塞米松（DEX）使其免疫抑制后，经腹腔接种委内瑞拉马脑炎（VEE）病毒的瓜希拉毒株。在病毒接种前3天和接种后10天，每天以500微克/千克体重的剂量给予褪黑素（MLT）。测定所有实验组（对照组、DEX组、DEX + MLT组、DEX + VEE组、DEX + VEE + MLT组、VEE组和MLT组）血清中的粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-2（IL-2）水平。在病毒接种后第6天，免疫抑制感染小鼠用MLT治疗组（DEX + VEE + MLT）的存活率从DEX + VEE组的0%显著提高到32.5%。到第10天，DEX + VEE + MLT组的存活率为10%，VEE组为0%。未观察到IL-2血清水平有变化。MLT使对照组和DEX处理小鼠的GM-CSF增加。在DEX处理的VEE病毒感染小鼠中，接种后第1天至第5天GM-CSF血清水平逐渐升高。相比之下，接种后第1天至第5天，用MLT治疗的免疫抑制感染小鼠的GM-CSF水平显著下降。在病毒接种后第5天，VEE组、DEX + VEE组和DEX + MLT + VEE组的脑病毒滴度未检测到差异。这些结果表明，MLT不抑制免疫抑制小鼠脑中VEE病毒的复制。
