Some studies report that hormone melatonin can be found in human milk, but the daily variation in colostrummelatonin is not available. This study verified the effects of milk collection time (diurnal/nocturnal) on colostralmelatonin levels and the ability of this hormone to modulate colostral phagocyte activity. Colostrum sampleswere collected from 30 mothers during the day and night, for a total of 60 samples. We determined melatoninlevels in colostrum and superoxide release and bacterial killing by colostral phagocytes. Melatonin levelswere higher in colostrum samples collected at night. Phagocytes in nocturnal colostrum samples increasedspontaneous superoxide release. In diurnal colostrum samples, mononuclear (MN) phagocytes increasedsuperoxide release when exposed to enteropathogenic Escherichia coli (EPEC), but not polymorphonuclear(PMN) phagocytes. Phagocytes exposed to both EPEC and melatonin had higher superoxide release,independent of phagocyte type and colostrum collection period. Phagocytosis rate was higher in colostrumsamples collected at night. In diurnal samples, EPEC killing by MN phagocytes was lower than by PMNphagocytes. Phagocytosis increased significantly in the presence of melatonin in both MN and PMN cells,irrespective of colostrum collection period. In response to melatonin, MN phagocytes from both diurnaland nocturnal samples increased bactericidal activity, whereas colostral PMN phagocytes increased it onlyin diurnal samples. The melatonin increased in the intracellular Ca2+ levels. The highest intracellular Ca2+release were found in MN phagocytes diurnal samples. These results confirm that melatonin levels in humancolostrum follow a day-night variation and increase phagocytic activity of colostral cells against bacteria

The present study characterized natural killer cells and cytokines in diabetic mothers, their placenta, and fetus. In the maternal blood from the hyperglycemic groups, the CD16+CD56− NK cells increased, whereas that of CD16+CD56+ decreased in gestational diabetes mellitus [GDM] group. Cord blood from type 2 diabetes [DM-2] showed a higher proportion of CD16+CD56− and CD16−CD56+. The placental extravillous layer of GDM and DM-2 showed an increase of CD16+CD56− cells and, irrespective of region, the proportion of CD16−CD56+ cells was higher in mild gestational hyperglycemia [MGH] and GDM and lower in DM-2. IL-2 was lower in maternal blood and IFN-γ higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ and low levels of IL-1β and IL-8, whereas the placental villous layer contained high levels of IL-17 and IFN-γ. The GDM group, irrespective of region, showed higher levels of IL-8. The DM-2 group, irrespective of region, placenta showed high levels of TNF-α, IL-17, and IFN-γ. The hyperglycemia produces an inflammatory environment with a high content of inflammatory cytokines and cells expressing CD16+.

The results obtained suggest that maternal hyperglycemia modifies the phenotypes of T cells and cytokines profile in maternal, cord blood and colostrum.

The effectiveness of hormones associated with polymeric matrices has amplified the possibility of obtaining new drugs to activate the immune system. Melatonin has been reported as an important immunomodulatory agent that can improve many cell activation processes. It is possible that the association of melatonin with polymers could influence its effects on cellular function. Thus, this study verified the adsorption of the hormone melatonin to polyethylene glycol (PEG) microspheres and analyzed its ability to modulate the functional activity of human colostrum phagocytes. Fluorescence microscopy and flow cytometry analyses revealed that melatonin was able to adsorb to the PEG microspheres. This system increased the release of superoxide and intracellular calcium. There was an increase of phagocytic and microbicidal activity by colostrum phagocytes when in the presence of melatonin adsorbed to PEG microspheres. The modified delivery of melatonin adsorbed to PEG microspheres may be an additional mechanism for its microbicidal activity and represents an important potential treatment for gastrointestinal infections of newborns.

Children are more susceptible to Giardia lamblia infection. Cells and hormones contained in human colostrum have an immunoprotective action against giardiasis, but the effects of advanced maternal age on these components are poorly understood. This study analyzed the colostrum of older women to determine melatonin and cortisol levels besides the participation of these hormones on the functional activity of phagocytes against G. lamblia. Colostrum samples were collected from younger (18 to 35 years old) and older (over 36 years old) lactating women. Colostrum samples were subjected to melatonin and cortisol determination, immunophenotyping, quantification of superoxide release, and assessment of phagocytic rate and microbicidal activity of phagocytes treated with hormones and in the presence of G. lamblia. Colostrum from mothers of advanced age contained higher melatonin and cortisol levels and a lower rate of cells expressing CD14 and CD15. In the colostru of these older mothers, melatonin increased superoxide release by phagocytes. In both groups, superoxide release by phagocytes treated with cortisol was higher in the presence of G. lamblia. In colostrum from mothers of advanced age, mononuclear (MN) phagocytes treated with melatonin showed higher phagocytosis of G. lamblia and higher microbicidal index. In younger mothers, MN and polymorphonuclear (PMN) colostrum phagocytes exhibited higher rates of G. lamblia elimination when treated with both melatonin and cortisol. In older mothers, cortisol and melatonin regulation for the functional activity of colostrum phagocytes against G. lamblia may represent an additional defense mechanism, relevant for the protection and treatment of parasitic infections in breastfed children.