Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis

Emami, Claudia N.; Chokshi, Nikunj K.; Wang, Jin; Hunter, Catherine J.; Guner, Yigit S.; Goth, Kerstin; Wang, Larry; Grishin, Anatoly; Ford, Henri R.

doi:10.1016/j.amjsurg.2011.08.016

Cited by 74 publications

(55 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…91 Pentoxifylline Intraperitoneal administration of pentoxifylline reduced the incidence and severity of NEC significantly in an animal model. 92 …”

Section: Interleukin-10mentioning

confidence: 99%

Prevention of necrotizing enterocolitis in preterm very low birth weight infants: Is it feasible?

Lin

Chang

Chung

et al. 2014

Journal of the Formosan Medical Association

View full text Add to dashboard Cite

Necrotizing enterocolitis (NEC) is still one of the most catastrophic intestinal emergencies in preterm very low-birth weight infants. Primary prevention of NEC should be the priority, since NEC frequently progresses from nonspecific signs, to extensive necrosis within a matter of hours with medical or surgical treatment, making successful treatment and secondary prevention difficult to achieve. Currently available strategies for primary prevention of NEC include antenatal glucocorticosteroids, breast milk feeding, cautious feeding strategy, fluid restriction and probiotics. Nonetheless, based on current research evidence, mixed flora probiotics, and/or breast milk feeding, would appear to be the most effective feasible methods in the prevention of NEC at present.

show abstract

“…91 Pentoxifylline Intraperitoneal administration of pentoxifylline reduced the incidence and severity of NEC significantly in an animal model. 92 …”

Section: Interleukin-10mentioning

confidence: 99%

Prevention of necrotizing enterocolitis in preterm very low birth weight infants: Is it feasible?

Lin

Chang

Chung

et al. 2014

Journal of the Formosan Medical Association

View full text Add to dashboard Cite

show abstract

“…Although we did observe a decrease in serum IL-10 following IAP administration, this did not reach statistical significance. IL-10 is believed to be a counterregulatory cytokine and the upregulation of IL-10 in NEC has been suggested to ameliorate mucosal inflammation and injury in NEC [32].…”

Section: Discussionmentioning

confidence: 99%

Intestinal Alkaline Phosphatase Prevents the Systemic Inflammatory Response Associated With Necrotizing Enterocolitis

Riggle

Rentea

Welak

et al. 2012

Journal of Surgical Research

View full text Add to dashboard Cite

Background-Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with an incidence of 0.5-2.4 cases per 1000 live births and a mortality rate between 10% and 50%. Neonates affected by NEC develop a septic injury that is associated with increased risk of neurological impairment due to intraventricular bleeding and chronic lung disease. Intestinal alkaline phosphatase (IAP) is an endogenous protein that has been shown to inactivate the endotoxin lipopolysaccharide (LPS), and has recently been used successfully as an adjunct to treat sepsis in adult patients. We tested the hypothesis that systemic, exogenous IAP will mitigate the inflammatory response as measured by serum levels of proinflammatory cytokines in a rat model of NEC.Methods-Newborn Sprague-Dawley rats were divided into groups. Control pups were dam fed. NEC was induced by feeding formula containing LPS and exposure to intermittent hypoxia. NEC pups were given intraperitoneal injections of 4 or 40 glycine units (U) of IAP or placebo twice daily. Intestine and serum was collected for cytokine analysis as well as measurement of alkaline phosphatase activity.Results-Systemic IAP administration significantly increased serum alkaline phosphatase activity in a dose-and time-dependent fashion. The proinflammatory cytokines tumor necrosis factor α, interleukin 6, and interleukin 1β were significantly increased in NEC rats versus controls on days 2 and 3. Importantly, treatment with 40 U systemic IAP decreased these proinflammatory cytokines back to near-control levels.Conclusions-Systemic IAP administration appears effective in mitigating the systemic inflammatory response associated with NEC, and may prove to be a valuable adjunctive treatment for NEC.

show abstract

“…It is tempting to speculate that intestinal macrophages in the GI tract following IL-1α exposure to the chorioamnion/skin might be responsible for the accumulation of T cells in the fetal gut. 36 This intestinal immune response at 6 days after IL-1α administration to the chorioamnion/skin appeared to have an anti-inflammatory character as upregulated mRNA levels of IL-10, a cytokine that has central role in maintaining gut wall integrity, 37,38 were detected and associated with the absence of epithelial damage in the fetal ileum.…”

Section: Il-1α-driven Fetal Gut Inflammationmentioning

confidence: 99%

Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep

Nikiforou

Kemp

Gorp

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

Chorioamnionitis, caused by intra-amniotic exposure to bacteria and their toxic components, is associated with fetal gut inflammation and mucosal injury. In a translational ovine model, we have shown that these adverse intestinal outcomes to chorioamnionitis were the combined result of local gut and pulmonary-driven systemic immune responses. Chorioamnionitis-induced gut inflammation and injury was largely prevented by inhibiting interleukin-1 (IL-1) signaling. Therefore, we investigated whether local (gut-derived) IL-1α signaling or systemic IL-1α-driven immune responses (lung or chorioamnion/skin-derived) were sufficient for intestinal inflammation and mucosal injury in the course of chorioamnionitis. Fetal surgery was performed in sheep to isolate the lung, gastrointestinal tract, and chorioamnion/skin, and IL-1α or saline was given into the trachea, stomach, or amniotic cavity 1 or 6 days before preterm delivery. Selective IL-1α exposure to the lung, gut, or chorioamnion/skin increased the CD3+ cell numbers in the fetal gut. Direct IL-1α exposure to the gut impaired intestinal zonula occludens protein-1 expression, induced villus atrophy, changed the expression pattern of intestinal fatty acid-binding protein along the villus, and increased the CD68, IL-1, and TNF-α mRNA levels in the fetal ileum. With lung or chorioamnion/skin exposure to IL-1α, intestinal inflammation was associated with increased numbers of blood leukocytes without induction of intestinal injury or immaturity. We concluded that local IL-1α signaling was required for intestinal inflammation, disturbed gut maturation, and mucosal injury in the context of chorioamnionitis. Intrauterine infection is the most frequent cause of preterm birth 1 before 28 weeks of gestation. 2 Chorioamnionitis, which is commonly caused by intrauterine bacterial infection, is defined as an inflammation of the fetal membranes, amniotic fluid and placenta. [3][4][5] Bacterial infection of the amniotic cavity results in direct exposure of the lung (by fetal breathing), gastrointestinal tract (by swallowing), skin, and chorioamnion to bacteria and their inflammatory components in the contaminated amniotic fluid. The fetal inflammatory response to chorioamnionitis is associated with multiorgan dysfunction, 6,7 which increase the incidence of periventricular leukomalacia, 8 bronchopulmonary dysplasia, 9 and necrotizing enterocolitis. 10,11 We have used a translational ovine model of chorioamnionitis to investigate the impact of intrauterine inflammation on fetal organs. Using this model, we have shown that intraamniotic (IA) delivery of Escherichia coli lipopolysaccharide (LPS) resulted in an acute inflammatory response in the chorioamnion and increased the influx of inflammatory cells in the respiratory tract within 5 h. 12,13 These immune alterations were rapidly followed by systemic inflammation at the same time point and fetal skin inflammation 12 h after LPS exposure. 13,14 The first signs of intestinal inflammation were detected 2 days after IA delivery of LPS, an...

show abstract

Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis

Cited by 74 publications

References 22 publications

Prevention of necrotizing enterocolitis in preterm very low birth weight infants: Is it feasible?

Prevention of necrotizing enterocolitis in preterm very low birth weight infants: Is it feasible?

Intestinal Alkaline Phosphatase Prevents the Systemic Inflammatory Response Associated With Necrotizing Enterocolitis

Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep

Contact Info

Product

Resources

About