Cytokines in Necrotizing Enterocolitis

Markel, Troy A.; Crisostomo, Paul R.; Wairiuko, George M.; Pitcher, Jeffrey M.; Tsai, Ben M.; Meldrum, Daniel R.

doi:10.1097/01.shk.0000192126.33823.87

Cited by 128 publications

(124 citation statements)

References 104 publications

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“…In our current model, the omission of anti-inflammatory cytokines provides a worst-case scenario with respect to the harmful effects of the inflammatory response. The qualitative relationships established in this study that indicate both beneficial and harmful effects of probiotics are still expected to hold in the presence of cytokines, but additional insight into the interplay of the immune response and probiotic treatment will require future modeling of cytokine populations [40,41].…”

Section: Additional Considerations and Conclusionmentioning

confidence: 99%

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Arciero

Ermentrout

Rubin

et al. 2009

Journal of Critical Care

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Background: Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species).

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Section: Additional Considerations and Conclusionmentioning

confidence: 99%

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Arciero

Ermentrout

Rubin

et al. 2009

Journal of Critical Care

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“…Several pro-inflammatory cytokines that mediate inflammatory cell recruitment through activation and amplification of the immune response in local host defense have been implicated in NEC including TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-18 [99][100][101] . Antiinflammatory cytokines modulate the host's inflammatory response and if they fail to achieve their goal, proinflammatory mediators can continue, resulting in tissue injury [4] .…”

Section: Cytokinesmentioning

confidence: 99%

Necrotizing enterocolitis: A multifactorial disease with no cure

Schnabl

Aerde²,

Thomson³

et al. 2008

WJG

160

120

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INTRODUCTIONNecrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates and remains one of the most common gastrointestinal emergencies in newborn infants [1] . Onset of NEC is often within the first three months of life and neonates who are of extremely low birth weight (< 1000 g) and under 28 wk gestation are the most susceptible [2] . Full term neonates account for 10% of all NEC cases while premature infants account for 90% [3] . With an incidence rate of 1%-5% for all newborns admitted to the NICU [1] , a prevalence of 7%-14% of very low birth weight infants (VLBW, 500-1500 g) [4] and a mortality rate approaching 20%-50% [5] , NEC continues to represent a significant clinical problem. In Canada, the incidence rate is 1.8 per 100 live births with a prevalence of 7% of VLBW infants [1] . Advances in obstetric and neonatal care have improved survival rates for smaller, more immature infants, and as more VLBW preterm infants survive the neonatal period, the population at risk for NEC increases [1] .No consistent association between sex, race, and rates of NEC has been identified. However, male VLBW infants and black infants are at greater risk of death [6] . Due to inadequate treatments and no effective preventative strategy, an estimated 20%-40% of babies with NEC require surgery [1] and 10%-30% experience significant morbidity including neurodevelopmental impairment, vision and hearing impairment, failure to thrive, feeding abnormalities, diarrhea, bowel obstruction, and short bowel syndrome [1,2,7] . The case fatality rate with surgical intervention is as high as 50% [1] . NEC is also a financial burden to the health care system with yearly hospital charges reported to be as high as $6.5 million in the US [8] . Thus, NEC continues to be an important health issue for preterm neonates. DIAGNOSIS Clinical signs and symptomsThe onset of NEC can occur suddenly within a few AbstractNecrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

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“…Therefore, its delayed occurrence after birth, its rapid onset, highly fulminant nature, and progression to death, as well as its severe morbidity, require identification of prospective new biomarkers specific for high NEC risk (Young et al 2009). Some studies have suggested the efficacy of several inflammatory mediators such as C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) measurements in the diagnosis of NEC (Pourcyrous et al 2005;Hallstrom et al 2006;Markel et al 2006;Evennett et al 2009;Cetinkaya et al 2010). These all have difficulties that limit their use.…”

mentioning

confidence: 99%

C5a, A Complement Activation Product, Is a Useful Marker in Predicting the Severity of Necrotizing Enterocolitis

Tayman

Tonbul

Kahveci³

et al. 2011

Tohoku J. Exp. Med.

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Necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal emergency, predominantly affecting low-birth weight, premature infants. Early clinical signs of NEC are nonspecific and the laboratory findings are not fully reliable. Its severe morbidities and rapid progression require the application of new biomarkers for early diagnosis and intervention. The complement activation product, C5a (anaphylatoxin) has been reported to be a contributing factor leading to mesenteric ischemia/reperfusion injury which is a predisposing factor in the pathogenesis of NEC. Therefore, our aim was to evaluate the efficacy of serial C5a measurements in the diagnosis and follow-up of NEC. Preterm infants, whose gestational age and weight matched each other, were grouped as controls (n = 23) and NEC (n = 22). Serum levels of C5a, serum amyloid-A (SAA), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured on the third day of life for the control group and on the day of diagnosis (1 st day), 3 rd and 7 th days of the NEC group. C5a, SSA, CRP, and IL-6 levels were significantly higher in the NEC patients compared to the control group (P < 0.05) in the follow-up. Additionally, serum levels of C5a were found to be more accurate than the other parameters for the prediction of death and requirement for surgery at the time of diagnosis (P < 0.05). In conclusion, C5a may be useful as a new marker for both diagnosis and follow-up of infants with NEC in combination with clinical and radiographical findings.

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Cytokines in Necrotizing Enterocolitis

Cited by 128 publications

References 104 publications

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Necrotizing enterocolitis: A multifactorial disease with no cure

C5a, A Complement Activation Product, Is a Useful Marker in Predicting the Severity of Necrotizing Enterocolitis

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