Melatonin, as an adjuvant‐like agent, enhances platelet responsiveness

Abstract

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.

Multiple Facets of Melatonin in Immunity: Clinical Applications

“…The same effect was found with a double dose of melatonin after which the titer of antibodies and the IgG levels were notably increased comparing to untreated vaccinated animals [ 247 ]. The administration of melatonin either via implants or injections also enhanced the platelet response to thrombin stimulation improving the percentage and rate of aggregation and lag time [ 248 ]. This effect was likely mediated by enhancement of thrombin-evoked Ca2+ mobilization, especially Ca2+ entry from the extracellular medium.…”

Melatonin: Buffering the Immune System

“…Double doses of melatonin notably increased antibody titers and IgG levels compared to untreated, vaccinated animals [283]. The administration of melatonin either via implants or injections also enhanced the platelet response to thrombin stimulation, improving the percentage and rate of aggregation and lag-time [284]. The beneficial effects of melatonin on the immune response to vaccination against Clostridium perfringens type D in sheep have also been described [285].…”

Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep

“…Here, we showed for the first time in sheep, the differences in plasma melatonin concentration between non-pregnant and pregnant sheep. As we showed previously, sheep in non-gestational state have an average plasma melatonin concentration of 15 pg/mL [8], considerably smaller than pregnant sheep (125 pg/mL) (Table 1). Differences in plasma melatonin concentration may be due to strong melatonin antioxidant properties, as well as, as previously postulated, high levels of melatonin during pregnancy may be one of the factors that reduce oxidative damage from ROS in the placenta and systemic endothelial cells [18-21].…”

“…Melatonin has been shown to exert a positive effect as an adjuvant of a number of vaccines [7-11]. Platelet function is also regulated by melatonin binding to high-affinity sites [12], which results in enhanced platelet responsiveness to physiological agonist and inducing beneficial effects on platelet function and haemostasis [8]. …”

“…Here we have investigated the effect of melatonin administration as an adjuvant of the C. perfringens vaccine administered prepartum on the immune response. In addition, we have explored whether vaccination against C. perfringens alters platelet function, as shown for the vaccine against Dichelobacter nodosus [8]. …”