title: Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus.
abstract: We determined the influence of melatonin (MLT) on the induction of interleukin (IL)-2, IL-1 beta, IL-4, tumour necrosis factor-alpha (TNF-alpha) and gamma interferon (IFN-gamma) on mice infected with the Venezuelan equine encephalomyelitis (VEE) virus. Levels of IFN-gamma in the MLT-treated group were significantly increased (P < 0.001) when compared with the control non-infected group from day 1 to 6 post-infection (p.i.), while in infected mice treated with 500 micrograms MLT/kg of bodyweight enhanced levels of IFN-gamma were evident from 4 to 6 days p.i. No differences were detected in the levels of IL-2 between the controls, the infected mice treated with MLT and the infected untreated group, from day 2 p.i. No changes in serum levels of IL-4 were detected. In infected mice treated with MLT, blood levels of IL-1 beta were elevated almost 10-fold from day 1 to day 6 p.i. when compared to the control, the infected and the non-infected MLT-treated mice (P < 0.001). A highly significant rise (P < 0.001) of TNF-alpha was found in infected mice treated with MLT, from day 1 to 6 p.i. when compared to the other groups. A significant rise (P < 0.001) was also evident in the infected non-MLT-treated group and a less pronounced rise in the non-infected mice treated with MLT when compared to controls. The blockade of IFN-gamma and TNF-alpha did not inhibit the protective effect of MLT but when IL-1 beta was neutralized, 100% of the infected mice died suggesting that IL-1 beta induced by MLT treatment is a target cytokine to generate an immune response against the viral infection.
authors.affiliation: Instituto de Investigaciones Clínicas Dr Américo Negrette, Facultad de Medicina, Universidad del Zulia, Apartado 1151, Maracaibo 4001-A, Venezuela. nvalero@luz.ve
authors.forename: Nereida
authors.initials: N
authors.lastname: Valero
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bonilla
authors.forename: Héctor
authors.initials: H
authors.lastname: Pons
authors.forename: Leonor
authors.initials: L
authors.lastname: Chacin-Bonilla
authors.forename: Florencio
authors.initials: F
authors.lastname: Añez
authors.forename: Luz Marina
authors.initials: LM
authors.lastname: Espina
authors.forename: Shirley
authors.initials: S
authors.lastname: Medina-Leendertz
authors.forename: Jorge
authors.initials: J
authors.lastname: García  Tamayo
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004685:Encephalomyelitis, Venezuelan Equine / Q000097:blood*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008550:Melatonin