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 i 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, imrnunoreactive 1L-10 in milk increased after treatment with sodium taurocholate. Bioactive IL-10 was demonstrated by the finding that human milk inhibited [%]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 There is recent evidence that the immune system in human milk is composed not only of direct-acting antimicrobial agents and antiinflammatory factors, but also of immunoregulators (1). The immunoregulators in early human milk secretions include the proinflammatory cytokines TNF-cr (concentrations,-620 + 183 pg/mL) (2), IL-1P (concentrations,-1130 ? 478 pg/mL) (3), IL-6 (concentrations,-151 i-89 pg/mL) (4, 5), and 1L-8 (concentrations,-3684-C 2910 pg/mL) (6). The patterns of the concentrations of these cytokines in human milk suggested that the the levels were physiologically significant. It was ascertained that the production of TNF-cr by human milk leukocytes could not be augmented by the addition of N-formyl-I.-methionyl-I.-leucyl-1.-phenylalanine or 4P-phorbol-12P-myristate-13a-acetate to those cells in culture (2). Thus, the low production of ILl (7) and TNF-a (2) by leukocytes in human milk further suggested that human milk contains factors that regulate synthesis of proinflammatory cytokines. Because of the above evidence and the antiinflammatory character of the protection afforded by human milk, we hypothesized that human milk contains antiinflammatory cytokines. One antiinflammatory cytokine, TGF-P2, had already been found in human milk (6, 8,

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.

Background Coronavirus disease (COVID-19) has been associated with adverse pregnancy outcomes. Due to the lack of effective treatments for COVID-19, it becomes imperative to assess the geographical differences and trends in the current clinical care and outcomes of COVID-19 in pregnant women. Methods A PubMed search was performed to screen articles reporting therapeutics and outcomes of confirmed COVID-19 in pregnant women prior to August 27, 2020. We performed searches, quality assessments of eligible studies, extracted and reported data according to PRISMA guidelines. Meta-analyses and cumulative meta-analyses of proportions were performed for estimating each outcome and their pattern over time respectively. Results One thousand two hundred thirty nine pregnant women with COVID-19 from 66 studies were analyzed. In case series analysis reflecting average-risk patients, the proportion of oxygen support, antibiotics, antivirals, and plasma therapy administration except for hydroxychloroquine was substantially higher in Asian studies (55, 78, 80, 6, and 0%) compared to the US (7, 1, 12, 0, and 7%) or European (33, 12, 14, 1, and 26%) studies, respectively. The highest preterm birth and the average length of hospital stay (35%, 11.9 days) were estimated in Asian studies compared to the US studies (13%, 9.4 days) and European studies (29%, 7.3 days), respectively. Even in case reports reflecting severe cases, the use of antivirals and antibiotics was higher in Asian studies compared to the US, Latin American, and European studies. A significant decline in the use of most therapeutics along with adverse outcomes of COVID-19 in pregnant women was observed. Conclusions Geographical differences in therapeutic practice of COVID-19 were observed with differential rates of maternal and clinical outcomes. Minimizing the use of some therapeutics particularly antibiotics, antivirals, oxygen therapy, immunosuppressants, and hydroxychloroquine by risk stratification and careful consideration may further improve maternal and clinical outcomes.

The production of IL-10 by human neonatal blood mononuclear leukocytes (BML) stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), 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-alpha was approximately 20 and approximately 15%, respectively, of adult BML. The combination of human recombinant TNF-alpha 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-alpha could not be ruled out, because TNF-alpha production by LPS-stimulated newborn BML and the expression of TNF-alpha 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-alpha and its receptors.