Our results support the hypothesis that the colostrum of diabetic mothers suffers biochemical and immunological alterations that affect the levels of its components.

The effects of secretory immunoglobulin A (SIgA) interaction with its specific Fcα receptors on colostral phagocytes needs further investigation, especially with respect to diabetic women. Accordingly, we studied the colostrum of hyperglycemic women to assess SIgA interactions with Fcα receptors of macrophages as well as the functional activity of these cells. The women were divided for colostrum sampling according to their glycemic status: normoglycemia (N = 51), mild hyperglycemia (N = 23), and diabetes (N = 25) groups. We determined the FcαR expression, the IgA on the surface and the surface-bound IgA in colostrum macrophages. We also evaluated the superoxide release and bactericidal killing of these cells. Colostral phagocytes expressed FcαR, contained IgA on the surface and are able to bind to purified SIgA. The bactericidal activity of colostral phagocytes from the hyperglycemic women was similar to that of normoglycemic only when SIgA was used as opsonin. Addition of a MoAb anti-human Fcα receptor resulted in a significant decrease of superoxide release and bacterial killing by macrophages when bacteria were opsonized with purified SIgA, suggesting an interaction between SIgA and FcαR. The stimulatory effects of SIgA on the functional activity of phagocytes therefore protect infants, especially of diabetic women, against intestinal infections.

This study was carried out with hyperglycemic pregnant women to investigate the transfer of antibody classes to newborns across the placenta or by colostrum and the functional activity of phagocytes in maternal blood, cord blood, and colostrum from diabetes mothers. Samples from maternal blood, cord blood, and colostrum were collected from 20 normoglycemic and 20 hyperglycemic pregnant women. We determined antibodies levels, superoxide release, phagocytosis and bactericidal activity of phagocytes. We demonstrated that IgG levels in cord blood were higher in the hyperglycemic group. IgA and IgM levels were higher in maternal than in cord blood samples. Plasma antibody levels were lower in hyper- than in normoglycemic women. The colostrum of diabetic mothers had lower IgA and IgG levels. Colostrum and maternal blood phagocytes when exposed to EPEC increased the superoxide release. Cord blood phagocytes of hyperglycemic group, independently of bacteria, had higher superoxide release. Colostrum and blood phagocytes from diabetic group exhibited some phagocytic and microbicidal activity in response to EPEC. Mononuclear phagocytes from cord blood had the lowest phagocytosis, and bactericidal activity for EPEC, regardless of glycemic status. These data showed that hyperglycemia altered IgG transfer across the placenta and decreases immunoglobulin levels in maternal blood and colostrum.

Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N = 38) and diabetic (N = 38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca2+ release by colostral phagocytes treated or not with 8-(Diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and incubated with melatonin and its precursor (N-acetyl-serotonin-NAS), antagonist (luzindole) and agonist (chloromelatonin-CMLT). Melatonin concentration was higher in colostrum samples from hyperglycemic than normoglycemic mothers. Melatonin stimulated superoxide release by colostral phagocytes from normoglycemic but not hyperglycemic women. NAS increased superoxide, irrespective of glycemic status, whereas CMTL increased superoxide only in cells from the normoglycemic group. Phagocytic activity in colostrum increased significantly in the presence of melatonin, NAS and CMLT, irrespective of glycemic status. The bactericidal activity of colostral phagocytes against enterophatogenic Escherichia coli (EPEC) increased in the presence of melatonin or NAS in the normoglycemic group, but not in the hyperglycemic group. Luzindole blocked melatonin action on colostrum phagocytes. Phagocytes from the normoglycemic group treated with melatonin exhibited an increase in intracellular Ca2+ release. Phagocytes treated with TMB-8 (intracellular Ca2+ inhibitor) decreased superoxide, bactericidal activity and intracellular Ca2+ release in both groups. The results obtained suggest an interactive effect of glucose metabolism and melatonin on colostral phagocytes. In colostral phagocytes from normoglycemic mothers, melatonin likely increases the ability of colostrum to protect against EPEC and other infections. In diabetic mothers, because maternal hyperglycemia modifies the functional activity of colostrum phagocytes, melatonin effects are likely limited to anti-inflammatory processes, with low superoxide release and bactericidal activity.

Immune response changes induced by diabetes are a risk factor for infections during pregnancy and may modify the development of the newborn's immune system. The present study analyzed colostrum and maternal and cord blood of diabetic women to determine (1) the levels of the cytokines IFN-γ and TGF-β and (2) phagocytic activity after incubation with cytokines. Methods. Colostrum and maternal and cord blood samples were classified into normoglycemic (N = 20) and diabetic (N = 19) groups. Cytokine levels, superoxide release, rate of phagocytosis, bactericidal activity, and intracellular Ca2+ release by phagocytes were analyzed in the samples. Irrespective of glycemic status, IFN-γ and TGF-β levels were not changed in colostrum and maternal and cord blood. In maternal blood and colostrum, superoxide release by cytokine-stimulated phagocytes was similar between the groups. Compared to spontaneous release, superoxide release was stimulated by IFN-γ and TGF-β in normoglycemic and diabetic groups. In the diabetic group, cord blood phagocytes incubated with IFN-γ exhibited higher phagocytic activity in response to EPEC, and maternal blood exhibited lower microbicidal activity. These data suggest that diabetes interferes in maternal immunological parameters and that IFN-γ and TGF-β modulate the functional activity of phagocytes in the colostrum, maternal blood, and cord blood of pregnant diabetic women.