RESUMO
BACKGROUND: Melatonin regulates several physiological processes and its powerful action as antioxidant has been widely reported. Melatonin acts modulating the immune system, showing a protective effect on the cardiovascular system and improving vaccine administration as an adjuvant-like agent. Here, we have investigated the role of melatonin as an adjuvant of the Clostridium perfringens vaccine in prepartum sheep and whether melatonin modulates platelet physiology during peripartum. RESULTS: The experiments were carried out in peripartum sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by ELISA and sheep platelet aggregation was monitored using an aggregometer. Here we demonstrated for the first time that plasma melatonin concentration were higher in pregnant (125 pg/mL) than in non-pregnant sheep (15 pg/mL; P < 0.05). Administration of melatonin prepartum did not significantly modify platelet function but significantly improved the immune response to vaccination against C. perfringens. CONCLUSION: Administration of melatonin as an adjuvant provides a significant improvement in the immune response to vaccine administration prepartum against C. perfringens.
Assuntos
Vacinas Bacterianas/imunologia , Infecções por Clostridium/veterinária , Melatonina/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Doenças dos Ovinos/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Animais , Vacinas Bacterianas/administração & dosagem , Infecções por Clostridium/prevenção & controle , Clostridium perfringens/imunologia , Implantes de Medicamento , Feminino , Esquemas de Imunização , Melatonina/sangue , Agregação Plaquetária/imunologia , Gravidez , Ovinos , Doenças dos Ovinos/microbiologiaRESUMO
Melatonin exerts immunomodulatory actions that enhance the magnitude and quality of immune responses specific for certain antigens; this has raised the possibility of using melatonin to design novel vaccine adjuvant systems. The present study investigated the effect of subcutaneous slow-release melatonin implants and subcutaneous melatonin injections on the responsiveness of circulating platelets in sheep after vaccination against Dichelobacter nodosus (A1 and C serotypes), the bacterium that causes ovine footrot, a major cause of lameness in sheep. The experiments were carried out in sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by radioimmunoassay, sheep platelet aggregation was monitored using an aggregometer and Ca2+ mobilization was determined by spectrofluorimetry using fura-2. Administration of melatonin either by implants or subcutaneous injections increased plasma melatonin concentrations, an effect that was found to be greater and more sustained when melatonin was administered via implants. Vaccination per se, as well as melatonin, increased the percentage and rate of platelet aggregation and reduced the lag-time in response to the physiological agonist thrombin, an effect that was found to be significantly greater when melatonin was administered to vaccinated animals. Melatonin enhanced thrombin-evoked Ca2+ release and entry and further increased Ca2+ mobilization observed in platelets from vaccinated sheep. These observations suggest that the use of melatonin, as a novel adjuvant, induces beneficial effects on platelet function and haemostasis, and opens new perspectives for therapeutic manipulation of immune responses to vaccination.
Assuntos
Adjuvantes Imunológicos , Vacinas Bacterianas/administração & dosagem , Plaquetas/metabolismo , Dichelobacter nodosus/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Melatonina/administração & dosagem , Agregação Plaquetária , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/sangue , Animais , Cálcio/metabolismo , Interpretação Estatística de Dados , Pododermatite Necrótica dos Ovinos/imunologia , Pododermatite Necrótica dos Ovinos/prevenção & controle , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Hemostasia , Melatonina/sangue , Melatonina/imunologia , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/prevenção & controle , Trombina/metabolismo , Vacinação/veterináriaRESUMO
The immunomodulatory functions mediated by melatonin support its use as vaccine adjuvant. Previously, we have demonstrated that melatonin enhances antibody responses in sheep vaccinated against Dichelobacter nodosus. Here, we analyze the effect of melatonin on T and B lymphocyte subsets in peripheral blood of sheep vaccinated against D. nodosus. We also compare the use of melatonin in implants and in injections. Melatonin administration either as implants or by injection produced higher antibody titers against A1 and C serotypes compared to those animals that received only the vaccine. These results support the use of melatonin as an adjuvant in vaccination against D. nodosus. Firstly, melatonin induces higher antibody titer than the vaccine alone, secondly, melatonin increase IgG+ B lymphocytes and CD4+ T lymphocytes in vaccinated sheep. These results suggest that melatonin enhances T CD4 cell activation and subsequently secondary humoral immune responses. Further studies are required to determine the mechanism underlining the immunomodulatory role of melatonin in the context of vaccination.
Assuntos
Linfócitos B/imunologia , Vacinas Bacterianas/imunologia , Linfócitos T CD4-Positivos/imunologia , Dichelobacter nodosus/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Melatonina/uso terapêutico , Doenças dos Ovinos/imunologia , Adjuvantes Imunológicos/uso terapêutico , Administração Cutânea , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Implantes de Medicamento , Feminino , Citometria de Fluxo/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Imunogenicidade da Vacina/efeitos dos fármacos , Imunoglobulina G/sangue , Melatonina/administração & dosagem , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/prevenção & controleRESUMO
Melatonin has been shown to exert immunomodularory properties with broad application in veterinary medicine. In previous work we have described that subcutaneous coadministration of melatonin to seeps vaccinated against two stumps of A1 and C strains of Dichelobacter nodosus enhanced both the antibody titer and serum IgG levels to A1 and C strains of D. nodosus compared to vaccinated animals not treated with melatonin. Following a similar protocol here we have investigated the effect of a higher dose of melatonin (36mg/animal) in the improvement of the immune response and in the possible oxidative/nitrosative stress produced during the immunization protocol. Our results show that footrot vaccine application induced nitrosative but not oxidative stress at 42 days post-vaccination, which was neutralized by melatonin administration. On the other hand, melatonin improved the immune response with respect to our previous data increasing the time of permanence of antibodies in serum, opening new perspectives for melatonin as prophylactic drug.
Assuntos
Vacinas Bacterianas/imunologia , Dichelobacter nodosus/imunologia , Pododermatite Necrótica dos Ovinos/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Melatonina/farmacologia , Doenças dos Ovinos/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Antioxidantes/farmacologia , Vacinas Bacterianas/farmacologia , Temperatura Corporal/imunologia , Preparações de Ação Retardada , Feminino , Pododermatite Necrótica dos Ovinos/imunologia , Pododermatite Necrótica dos Ovinos/microbiologia , Glutationa/sangue , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Malondialdeído/sangue , Nitratos/sangue , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/microbiologia , Vacinação/veterináriaRESUMO
Melatonin has been shown to exert immunomodulatory properties with broad application in veterinary medicine. Here we have investigated the effect of exogenous melatonin in the improvement of the immune response to administration of an immune-preparation of two stumps of A1 and C strains of Dichelobacter nodosus in sheep. Subcutaneous administration of melatonin enhanced plasma levels of melatonin from days 42 to 120. Administration of melatonin to vaccinated animals enhanced both the titer of antibodies and serum IgG levels to A1 and C strains of D. nodosus compared to vaccinated animals not treated with melatonin. Our results suggest that melatonin increased the immune response to vaccination and open new perspectives in the design of prophylactic strategies.