Melatonin prolongs survival of immunodepressed mice infected with the Venezuelan equine encephalomyelitis virus

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.