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 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,

Early nutrition and the development of immune function in the neonate

“…Further studies have shown that TGFβ is rapidly taken up by neonatal tissues, including the intestine, which suggest that this protein may have an important role in postnatal development (Letterio et al 1994) and may play a crucial role in regulating inflammatory immune responses generated in vulnerable neonatal tissues. Interleukin 10 also inhibits pro-inflammatory cytokine release, limits Th1 reactions and interacts synergistically with TGFβ to augment IgA synthesis (Garofalo et al 1995). Hence, the function of interleukin 10 and TGFβ in human milk is possibly to enhance non-inflammatory defence mechanisms at mucosal surfaces and to suppress potentially damaging inflammatory immune reactions.…”

“…The immuno-suppressive effect may be due to the possibility that secretory IgA reduces the uptake of dietary and bacterial antigens, and therefore reduces their contact with the GALT (Brandtzaeg, 1998). Breast milk also contains immuno-suppressive factors such as interleukin 10 and transforming growth factor β (TGFβ) (Letterio et al 1994;Garofalo et al 1995). The immuno-suppressive properties of breast milk may facilitate tolerance induction to harmless food antigens and antigens associated with commensal bacteria (Brandtzaeg, 1998), and may explain why breast-fed infants have a lower incidence of foodrelated allergies (Saarinen & Kajosaari, 1995).…”

“…Lactoferrin and fragments of lactoferrin have been shown to inhibit the endotoxininduced interleukin 6 release from human monocytic cells (Mattsby-Baltzer et al 1996). The cytokines interleukin 10 and TGFβ have been documented in maternal milk, and are also recognized to have immuno-suppressive and antiinflammatory activity (Letterio et al 1994;Garofalo et al 1995). Maternal TGFβ has been shown to be important to the survival of TGFβ-null mice, and functions by reducing the diffuse and lethal inflammation caused by gene disruption (Letterio et al 1994).…”

Role of breast-feeding in managing malnutrition and infectious disease

“…Although this possibility has not been investigated, cytokines may be similarly transported in milk and released by lysis of the macrophages in the gut. Measurable concentrations of both interleukin (IL)-10 ( Garofalo et al 1995) and transforming growth factor-β (Filteau et al 1999a) increased in milk after treatment of the samples with bile salts, suggesting these cytokines may be sequestered in the lipid globule and released in the infant intestine. Transforming growth factor-β is the cytokine for which perhaps the best evidence exists for its survival and indeed, activation, during passage through the infant gut (Ishizaka et al 1994;Letterio et al 1994).…”

“…Fat globules can bind potential pathogens and prevent their attachment to infant cells, a first step in infection (Peterson et al 1998). Fat globules may sequester and thus protect specific milk immune factors during passage through the infant stomach (Garofalo et al 1995;Filteau et al 1999a;Schroten et al 1999). Once hydrolysed from triacylglycerols, milk fatty acids can damage bacteria by disrupting their cell membranes (Hamosh, 1998).…”