The Role of Interleukin-6 and Interleukin-8 Circulating Cytokines in Differentiating between Feeding Intolerance and Necrotizing Enterocolitis in Preterm Infants

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To describe the circulating levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-8 in stable premature infants, infants with suspect necrotizing enterocolitis (NEC)/feeding intolerance (FI), and infants with proven NEC and to determine whether combinations of markers could provide a diagnostic tool for differentiating between benign FI and NEC.


Seventy infants were enrolled in a prospective study performed in two university neonatal intensive care units. Thirty-five matched controls (CON), 23 infants with FI or suspect NEC, and 12 infants with definitive and surgical NEC were studied. The pro-inflammatory cytokine (TNF-α, IL-6, and IL-8) levels were measured at the onset of FI or NEC, or during week 2 to 3 for CON.


There was no statistically significant difference in TNF-α levels among the three patient groups. IL-6 and IL-8 were significantly elevated in NEC group as compared with CON (p > 0.001), and in NEC group as compared with FI/suspect NEC. There was no significant difference in individual plasma levels of IL-6 or IL-8 between the CON and FI. The combined serum levels of IL-6 and IL-8 was more predictive of NEC stage II/III (area under the curve = 0.80; 95% confidence interval [CI]: 0.69-0.92; p < 0.0001).


IL-6 and IL-8 were significantly elevated in infants with definitive surgical NEC but not those with FI. The combined level of IL-6 and IL-8 may be useful for distinguishing infants with suspect NEC/FI from those with NEC.

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