Sadhana Chheda

Interleukin-10 in human milk.

ABSTRACT: The concentrations of immunoreactive IL-10 in the aqueous fraction of 20 specimens of human milk obtained during the first 80 h of lactation and stored at –60°C ranged from 66 to 9301 pg/mL (mean ± SD, 3304 ± 3127 pg/mL). IL-10 was present also in the lipid layer of milk. Gel filtration revealed that IL-10 was located in a high molecular weight fraction, where certain other cytokines in human milk have been found. In addition, immunoreactive IL-10 in milk increased after treatment with sodium taurocholate. Bioactive IL-10 was demonstrated by the finding that human milk inhibited [3H]thymidine uptake by human blood lymphocytes and that inhibition was partly overcome by concomitant incubation with antibodies to human IL-10. IL-10 mRNA but no protein product was found in cultured human mammary epithelial cells. Some IL-10 was associated with preparations of human milk leukocytes, but the data did not suggest that the cells were producing the cytokine. Bioactive IL-10 in a possible protected compartment suggests that IL-10 in human milk may have immunomodulating, antiinflammatory effects on the alimentary tract of the recipient infant.

Decreased Interleukin-10 Production by Neonatal Monocytes and T Cells: Relationship to Decreased Production and Expression of Tumor Necrosis Factor-α and Its Receptors

The production of IL-10 by human neonatal blood mononuclear leukocytes(BML) stimulated with lipopolysaccharide (LPS), tumor necrosis factor-α(TNF-α), antibodies to CD3, or phorbol 12-myristate 13-acetate (PMA) was measured. The production of IL-10 by neonatal BML cultured with LPS or TNF-α was ≈20 and ≈15%, respectively, of adult BML. The combination of human recombinant TNF-α and LPS failed to augment IL-10 production in neonatal BML. The decreased production of IL-10 by neonatal leukocytes was not due to an autocrine feedback mechanism because only low concentrations of IL-10 were found in newborn sera. A connection with TNF-α could not be ruled out, because TNF-α production by LPS-stimulated newborn BML and the expression of TNF-α receptors on newborn monocytes were reduced. Mean ± SD of concentrations of IL-10 in supernatants from adult and neonatal BML after stimulation with antibodies to human CD3 for 48 or 72 h were 914 ± 386 and 178 ± 176 pg/mL, respectively (p < 0.0001). In experiments with enriched populations of neonatal T cells, the addition of PMA failed to augment IL-10 production. This suggested that newborn T cells may be in a different state of activation than adult T cells Thus, IL-10 production in neonatal monocytes and T cells is reduced and this study suggests that the reduction may be secondary in part to regulatory processes involving TNF-α and its receptors.

Evolution of immunologic functions of the mammary gland and the postnatal development of immunity

Physiologic delays in production of immune factors occur in mammals including Homo sapiens. This finding is counter to a basic tenet of biologic evolution, because such delays increase the risk of infections. The disadvantage is, however, offset by defense factors in milk of the species in whom the developmental delay occurs. Reciprocal relationships between the production of immune factors by the lactating mammary gland and the production of those defense agents during early infancy are found in all investigated mammalian species. Thus, the evolution of these processes is closely related. Certain immunologic components of milk are highly conserved, whereas others vary according to the species. The variations most likely evolved by genetic mutations and natural selection. In addition, the immune composition of mammalian milks is associated with developmental delays in the same immunologic agents. Furthermore, most closely related mammals, such as humans and chimpanzees, are most similar in the defense agents in their milks and the corresponding developmental delays in their immune systems. Defense factors in human milk include antimicrobial agents (secretory IgA, lactoferrin, lysozyme, glycoconjugates, oligosaccharides, and digestive products of milk lipids), antiinflammatory factors (antioxidants, epithelial growth factors, cellular protective agents, and enzymes that degrade mediators of inflammation), immunomodulators (nucleotides, cytokines, and antiidiotypic antibodies), and leukocytes (neutrophils, macrophages, and lymphocytes). Because of a lack of geographic/ethnic variation in the immunologic composition of human milk and corresponding immunologic delays in infants, these evolutionary processes seem stable. This is supported by investigations of diverse populations that indicate that this evolutionary outcome is highly beneficial to human infants.

Cytokines in human milk: Properties and potential effects upon the mammary gland and the neonate

Epidemiologic and immunologic studies of breastfed and nonbreastfed infants and investigations of certain biologic activities in human milk led to the identification of immunomodulating agents in human milk. Among them were the cytokines interleukin-1β (IL-1β); IL-6, IL-8, IL-10, granulocyte-colony stimulating factor, macrophage-colony stimulating factor (M-CSF), tumor necrosis factor-α, interferon-γ, epithelial growth factor (EGF), transforming growth factor-α (TGF-α), and TGF-β2. Inteferon-γ may originate from T cells in milk; EGF, TGF-α, TGF-β, M-CSF, IL-6, and IL-8 may be produced by mammary gland epithelium. Based upon their known functions, we hypothesize that cytokines influence the development and immunologic function of the mammary gland and the neonate. Thosein vivo functions remain to be defined by future investigations.

Congenital brucellosis in a premature infant.

DOI: 10.14744/hnhj.2018.78055 Haydarpasa Numune Med J 2019;59(4):399–401 hnhtipdergisi.com HAYDARPAŞA NUMUNE MEDICAL JOURNAL

Deficient quantitative expression of CD45 isoforms on CD4+ and CD8+ T cell subpopulations and subsets of CD45RAlowCD45ROlow T cells in newborn blood

Deficiencies in the quantitative expression of CD45RA and CD45RO on CD4+ and CD8+ T cells and in a population of CD45RA(low)CD45RO(low) T cells in blood from term newborn infants were found by flow cytometry. The relative frequencies of CD45RO on CD4+ T cells from adults and newborn infants were 72 and 58%, respectively. However, in newborn infants greater than 70% of T cells expressing CD45RO also expressed CD45RA. In addition, the quantitative expression of CD45RA and CD45RO on newborn T cells was significantly less than that found on adult blood T cells.

DECREASED PRODUCTION OF IL-10 BY NEWBORN BLOOD MONOCYTES: RELATIONSHIP TO TNF-|[alpha]| AND ITS RECEPTORS. |[bull]| 1707

Background: We previously showed that the production of IL-10 (an important anti-inflammatory cytokine) by newborn monocytes is decreased. We questioned whether this was due to a decreased production of other cytokines such as TNF-α that enhance the production of IL-10, or to an impaired ability of these cells to be activated by these cytokines.