Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis

Fituch, C. C.; Palkowetz, Kimberly H.; Goldman, Armond S.; Schanler, Richard J.

doi:10.1080/08035250410022314

Cited by 24 publications

(4 citation statements)

References 17 publications

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“…Specifically, IL-10 is present in human breast milk, and Fituch et al . have demonstrated that premature infants who developed NEC despite receiving maternal milk feedings had mothers with lower concentrations of IL-10 in their breast milk [58].…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus (LGG) Regulates IL-10 Signaling in the Developing Murine Colon through Upregulation of the IL-10R2 Receptor Subunit

et al. 2012

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The intestinal microflora is critical for normal development, with aberrant colonization increasing the risk for necrotizing enterocolitis (NEC). In contrast, probiotic bacteria have been shown to decrease its incidence. Multiple pro- and anti-inflammatory cytokines have been identified as markers of intestinal inflammation, both in human patients with NEC and in models of immature intestine. Specifically, IL-10 signaling attenuates intestinal responses to gut dysbiosis, and disruption of this pathway exacerbates inflammation in murine models of NEC. However, the effects of probiotics on IL-10 and its signaling pathway, remain poorly defined. Real-time PCR profiling revealed developmental regulation of MIP-2, TNF-α, IL-12, IL-10 and the IL-10R2 subunit of the IL-10 receptor in immature murine colon, while the expression of IL-6 and IL-18 was independent of postnatal age. Enteral administration of the probiotic Lactobacillus rhamnosus GG (LGG) down-regulated the expression of TNF-α and MIP-2 and yet failed to alter IL-10 mRNA and protein expression. LGG did however induce mRNA expression of the IL-10R2 subunit of the IL-10 receptor. IL-10 receptor activation has been associated with signal transducer and activator of transcription (STAT) 3-dependent induction of members of the suppressors of cytokine signaling (SOCS) family. In 2 week-old mice, LGG also induced STAT3 phosphorylation, increased colonic expression of SOCS-3, and attenuated colonic production of MIP-2 and TNF-α. These LGG-dependent changes in phosphoSTAT3, SOCS3, MIP-2 and TNF-α were all inhibited by antibody-mediated blockade of the IL-10 receptor. Thus LGG decreased baseline proinflammatory cytokine expression in the developing colon through upregulation of IL-10 receptor-mediated signaling, most likely due to the combined induction of phospho-STAT3 and SOCS3. Furthermore, LGG-dependent increases in IL-10R2 were associated with reductions in TNF-α, MIP-2 and disease severity in a murine model of intestinal injury in the immature colon.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus (LGG) Regulates IL-10 Signaling in the Developing Murine Colon through Upregulation of the IL-10R2 Receptor Subunit

et al. 2012

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“…Animal models of NEC also show that maternal milk can reduce NEC severity while increasing intestinal IL-10 66 . Human infants whose mothers have low levels of IL-10 are at increased risk for NEC 67 and probiotics may regulate IL-10 signaling in the immature gut 68 . TGF-β is also thought to regulate the inflammatory response 69 and promote wound healing 70,71 .…”

Section: Passive Immunity In Necmentioning

confidence: 99%

Pathogenesis of NEC: Role of the innate and adaptive immune response

Denning

Bhatia

Kane

et al. 2017

Seminars in Perinatology

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Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC.

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“…117) and lower IL-10 abundance in breast milk correlates with increased human NEC incidence (Ref. 118). …”

Section: Mediators Of Innate Immunitymentioning

confidence: 99%

The immunological landscape in necrotising enterocolitis

Cho

Berger

Nold-Petry

et al. 2016

Expert Rev. Mol. Med.

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Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.

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Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis

Cited by 24 publications

References 17 publications

Lactobacillus rhamnosus (LGG) Regulates IL-10 Signaling in the Developing Murine Colon through Upregulation of the IL-10R2 Receptor Subunit

Lactobacillus rhamnosus (LGG) Regulates IL-10 Signaling in the Developing Murine Colon through Upregulation of the IL-10R2 Receptor Subunit

Pathogenesis of NEC: Role of the innate and adaptive immune response

The immunological landscape in necrotising enterocolitis

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