Comprehensive Evaluation of 11 Cytokines in Premature Infants with Surgical Necrotizing Enterocolitis

Abstract

ObjectiveA prospective study to investigate the pattern of pro- and anti-inflammatory cytokine responses in neonates with surgical necrotizing enterocolitis (NEC) and identify those cytokines being the most promising for future research.MethodsA panel of 11 different cytokines were measured in 9 infants with proven NEC and compared with 18 age-matched healthy neonates.ResultsThe serum concentrations of the interleukins (IL)-6, IL-8, and IL-10 were significantly (32–fold to 56-fold) higher in NEC infants compared with controls. In contrast, IL-5, IFN gamma, IL-4 and IL-2 showed slightly (1.4-fold to 5.9-fold) lower levels in the NEC samples. However, these cytokines showed a very low absolute concentration in infants with NEC and in controls. The sum of the serum concentrations of IL-6, IL-8 and IL-10 was able to clearly separate infants with NEC from control samples. IL-1 beta and TNF-alpha showed no statistically different levels. The serum levels of TNF-beta and IL-12p70 were below the detection limit in more than 50% of all samples per group.ConclusionIn spite of strong local inflammation only three out of eleven cytokines (IL-6, IL-8, and IL-10) showed strongly increased serum levels indicating an important role of them in the pathogenesis of NEC. At least two of these three cytokines were elevated in every single NEC patient. Thus, longitudinal monitoring of combined IL-8, IL-6, and IL-10 levels could reveal their potency in being clinical relevant markers in NEC.

Inflammatory signaling in NEC: Role of NF-κB, cytokines and other inflammatory mediators

“…When examined by in situ hybridization, human NEC tissues were found to have a marked increase in TNF-alpha mRNA in Paneth cells, as well as in infiltrating eosinophils and macrophages 62 . However, TNFα does not appear consistently elevated in serum samples of patients with NEC 36, 37, 45, 63 . Increased intestinal TNF-alpha levels were found in hypoxia/reoxygenation-induced bowel injury in neonatal rats 64 but not in a neonatal rat NEC model 57 and in an acute intestinal injury model (Our lab unpublished data, 2008).…”

Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis

“…There has been limited information, however, on whether cytokine measurements can be useful in diagnosis or risk assessment in NEC. Using a cytokine array only, IL-10, IL-8, and IL-6 were shown to be significantly higher in surgical NEC than in matched controls [18]. Others have reported similar findings on IL-6 and IL-8.…”

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

“…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 …”