Inflammatory Cytokine mRNAs in Surgical Specimens of Necrotizing Enterocolitis and Normal Newborn Intestine

Viscardi, Rose M.; Lyon, Nancy H.; Sun, Chen‐Chih J.; Hebel, J. Richard; Hasday, Jeffrey D.

doi:10.1080/15513819709168731

Cited by 65 publications

(29 citation statements)

References 35 publications

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“…Elevated IL-8/CXCL8, IL-6, and IL-18 levels have noted previously during NEC (3–6,37) and are adversely associated with disease severity and with short-term survival in NEC (4,38). IL-6 has a shorter half-life and may be detectable only for short periods after onset of NEC (39), whereas IL-8/CXCL8 levels may show sustained elevation and correlate with the severity of illness over a period of time (5).…”

Section: Discussionmentioning

confidence: 61%

“…Several cross-sectional studies show that NEC is associated with increased expression of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β, IL-6, and IL-8/CXC-motif ligand 8 (CXCL8) in both plasma and affected tissues (3–7). These cytokines are potential therapeutic targets in NEC because (a) preclinical evidence indicates that these cytokines can disrupt the epithelial barrier and augment intestinal injury (8); and (b) monoclonal antibodies and/or small molecule inhibitors are now available that can block the effect of these inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

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Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants

et al. 2014

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Background The goal was to identify cytokines associated with necrotizing enterocolitis (NEC). Based on our earlier reports of decreased tissue expression of transforming growth factor (TGF)-β, we hypothesized that infants with NEC also have low blood TGF-β levels. We further hypothesized that because fetal inflammation increases the risk of NEC, infants who develop NEC have elevated blood cytokine levels in early neonatal period. Methods Data on 104 extremely low birth weight (ELBW) infants with NEC and 893 without NEC from 17 centers were analyzed. Clinical information was correlated with blood cytokine levels on postnatal day 1 (D1), D3, D7, D14, and D21. Results Male gender, non-Caucasian/non-African-American ethnicity, sepsis, lower blood TGF-β and interleukin (IL)-2, and higher IL-8 levels were associated with NEC. The NEC group had lower TGF-β levels than controls since D1. The diagnosis of NEC was associated with elevated IL-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1/CC-motif ligand (CCL)-2, macrophage inflammatory protein-1β/CCL3, and C-reactive protein. Conclusions Clinical characteristics, such as gender and ethnicity, and low blood TGF-β levels are associated with higher risk of NEC. Infants who developed NEC did not start with high blood levels of inflammatory cytokines, but these rose mainly after the onset of NEC.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants

et al. 2014

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“…infantis secretions on the IL-1β-induced inflammatory response in premature human enterocytes. IL-1β is an important inflammatory cytokine associated with the pathogenesis of NEC and functions by mediating inflammatory cell recruitment and amplifying the innate immune response via enterocyte signaling [26,27]. The gut is colonized with trillions of beneficial commensal microorganisms which normally maintain a mutually beneficial symbiotic relationship with the host.…”

Section: Discussionmentioning

confidence: 99%

The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4

et al. 2017

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Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC). NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother’s expressed breast milk or ingesting selective probiotic organisms. Vaginally delivered, breast fed newborns develop health promoting bacteria (“pioneer” bacteria) which preferentially stimulate intestinal host defense and anti-inflammation. One such “pioneer” organism is Bacteroides fragilis with a polysaccharide (PSA) on its capsule. B. fragilis has been shown developmentally in intestinal lymphocytes and dendritic cells to produce a balanced T-helper cell (TH1/TH2) response and to reduce intestinal inflammation by activity through the TLR2 receptor stimulating IL-10 which inhibits IL-17 causing inflammation. No studies have been done on the role of B. fragilis PSA on fetal enterocytes and its increased inflammation. Accordingly, using human and mouse fetal intestinal models, we have shown that B. fragilis with PSA and PSA alone inhibits IL-1β-induced IL-8 inflammation in fetal and NEC intestine. We have also begun to define the mechanism for this unique inflammation noted in fetal intestine. We have shown that B. fragilis PSA anti-inflammation requires both the TLR2 and TLR4 receptor and is in part mediated by the AP1 transcription factor (TLR2) which is developmentally regulated. These observations may help to devise future preventative treatments of premature infants against NEC.

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“…At the tissue level, surgically-resected specimens of NEC consistently show increased mRNA expression of interleukin (IL)-1B, IL8/chemokine CXC-motif ligand (CXCL)-8, and tumor necrosis factor (TNF). 83–85 Many existing clinical studies on tissue expression of cytokines in human NEC are constrained by the limited selection of analytes. To obtain more comprehensive information on cytokine expression in NEC, we analyzed microarray data from surgically-resected specimens of bowel affected by NEC vs. uninflamed neonatal intestine resected for intestinal obstruction/during ileostomy repair ( n = 4 each; Fig 2).…”

Section: What Is the Role Of Cytokines In The Pathogenesis Of Nec?mentioning

confidence: 99%

“…89 Several other studies have also recorded elevated serum IL-6, IL-8/CXCL8, IL-10, and IL-18 concentrations during NEC. 83,87,91–95 IL-6 has a short half-life and may be detectable only for short periods after onset of NEC, 96 whereas IL-8/CXCL8 levels show sustained elevation 87 and correlate with the extent of NEC ( NEC totalis ), the need for surgical resection of bowel, and higher 60-day mortality. 91,94,97–99 …”

Section: What Is the Role Of Cytokines In The Pathogenesis Of Nec?mentioning

confidence: 99%

Cytokines and growth factors in the developing intestine and during necrotizing enterocolitis

MohanKumar¹,

Namachivayam²,

Ho³

et al. 2017

Seminars in Perinatology

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Cytokines and growth factors play diverse roles in the uninflamed fetal/neonatal intestinal mucosa and in the development of inflammatory bowel injury during necrotizing enterocolitis (NEC). During gestational development and the early neonatal period, the fetal/premature intestine is exposed to high levels of many “inflammatory” cytokines and growth factors, first via swallowed amniotic fluid in utero and then, after birth, in colostrum and mother’s milk. This article reviews the dual, seemingly counter-intuitive roles of cytokines, where these agents play a “trophic” role and promote maturation of the uninflamed mucosa, but can also cause inflammation and promote intestinal injury during NEC.

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Inflammatory Cytokine mRNAs in Surgical Specimens of Necrotizing Enterocolitis and Normal Newborn Intestine

Cited by 65 publications

References 35 publications

Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants

Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants

The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4

Cytokines and growth factors in the developing intestine and during necrotizing enterocolitis

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