Immune regulatory cytokines in the milk of lactating women from farming and urban environments

Paediatric Department, University of Verona, Verona, Italy.
Pediatric Allergy and Immunology (Impact Factor: 3.4). 09/2010; 21(6):977-82. DOI: 10.1111/j.1399-3038.2010.00995.x
Source: PubMed


Children living on farms have fewer allergies. It is unclear whether breastfeeding in different environments contributes to preventing allergies by exposing offspring to different cytokines that can modulate immune responses. The aim of this study was to quantify and compare levels of Transforming Growth Factor-beta1 (TGF-beta1) and Interleukin-10 (IL-10) in the colostrum and mature milk of mothers living in towns at sea level (references) and mothers on farms. Milk samples were collected within 3 days postpartum (colostrum) and at the first month of the baby's life (mature milk). Sixty-nine reference mothers and 45 farm mothers participated in the study. TGF-beta1 concentrations were significantly higher both in the colostrum (p < 0.05) and in mature milk (p < 0.05) of farm mothers. In the reference mothers, a significant decrease in TGF-beta1 concentrations was observed between colostrum (650, range 0-8000 pg/ml) and mature milk (250, range 0-8000 pg/ml) (p < 0.05). In farm mothers, TGF-beta1 concentrations were 1102 pg/ml (range 0-14,500) in colostrum and remained high in mature milk (821 pg/ml, range 0-14,650). IL-10 concentrations were higher in the mature milk of farm mothers (p < 0.05). No significant differences in IL-10 were observed between colostrum and mature milk in the control group (15 pg/ml, range 0-1800, and 0 pg/ml, range 0-230) or in farm mothers (9.5 pg/ml, range 0-1775, and 14.2 pg/ml, range 0-930), respectively. Exposure to a farm environment is associated with higher concentrations of TGF-beta1 and IL-10 in breast milk when compared to exposure to an urban environment. Higher cytokine concentrations in breast milk may influence early modulation of the development of an immune response, leading to a reduced prevalence of allergy-related diseases in farm children.

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    • "We also observed variation in EGF as a negative function of infant age (Figure 4B), a result that agrees well with earlier studies (Donovan and Odle 1994). Perhaps importantly, we observed relatively elevated levels of TGF-2 in the milk of Aeta women, suggesting a greater exposure to infectious pathogens (Amoudruz et al. 2009; Peroni et al. 2010); however, median levels in Aeta and Ilocano milks (2,419 and 1,644 pg/ml, respectively) were lower than mean values from Mali (3,727 pg/ml) and Sweden (3,703 pg/ml) (Holmlund et al. 2010). Such a difference highlights the potential for global variation in the baseline values of some cytokines (McDade et al. 2009). "
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    ABSTRACT: Early growth cessation and reproduction are predicted to maximize fitness under conditions of high adult mortality, factors that could explain the pygmy phenotype of many rainforest hunter-gatherers. This life-history hypothesis is elegant but contentious in part because it lacks a clear biological mechanism. One mechanism stems from the field of human immunological ecology and the concept of inflammation "memory" across the life cycle and into subsequent generations. Maternal exposures to disease can influence immunological cues present in breast milk; because maternal provisioning via lactation occurs during critical periods of development, it is plausible that these cues can also mediate early growth cessation and small body size. Such epigenetic hypotheses are difficult to test, but the concept of developmental programming is attractive because it could explain how the stature of a population can change over time, in terms of both secular increases and rapid intergenerational decreases. Here we explore this concept by focusing on the Aeta, a population of former hunter-gatherers, and the Ilocano, a population of rice farmers. We predicted that Aeta mothers would produce breast milk with higher concentrations of four bioactive factors due to high infectious burdens. Further, we predicted that the concentrations of these factors would be highest in the cohort of women born in the early 1990s, when exposure to infectious disease was acute following the eruption of Mount Pinatubo in June 1991. We analyzed levels of adiponectin, C-reactive protein, and epidermal growth factor in the milk of 24 Aeta and 31 Ilocano women and found no detectable differences, whereas levels of transforming growth factor-?2 were elevated among the Aeta, particularly as a function of maternal age. We found no difference between cohorts divided by the volcanic eruption (n = 43 born before, n = 12 born after). We discuss the implications of our findings for the terminal investment hypothesis and we suggest that the historical ecology of the Aeta is a promising model system for testing epigenetic hypotheses focused on the evolution of small body size.
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    • "Breast feeding is another way by which the neonatal immunity is affected, through the transfer of nutrients and bioactive factors present in breast milk, such as antibodies, soluble CD14, cytokines, immune cells and other immuno-active compounds (Hosea Blewett et al. 2008). Interestingly, the presence of immunological factors in breast milk can be influenced by maternal environment, such as shown in a study of Italian mothers living in non-farm or farm areas (Peroni et al. 2010). In this study the levels of TGF-β1, an anti-inflammatory cytokine, in breast milk from the farm-group was higher and more sustained than the levels in breast milk from the non-farm group, regardless of maternal atopic status. "
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    ABSTRACT: The shaping of a child's immune system starts in utero, with possible long-term consequences in later life. This review highlights the studies conducted on the development of the immune system in early childhood up to school-age, discussing the impact that environmental factors may have. Emphasis has been put on studies conducted in geographical regions where exposure to micro-organisms and parasites are particularly high, and the effect that maternal exposures to these may have on an infant's immune responses to third-party antigens. In this respect we discuss the effect on responses to vaccines, co-infections and on the development of allergic disorders. In addition, studies of the impact that such environmental factors may have on slightly older (school) children are highlighted emphasizing the need for large studies in low to middle income countries, that are sufficiently powered and have longitudinal follow-up components to understand the immunological footprint of a child and the consequences throughout life.
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