Interleukin-6-174-genotype, sepsis and cerebral injury in very low birth weight infants

Abstract

We investigated the association between the interleukin 6 (IL-6)-174-genotype and unfavorable outcomes in preterm infants since it has been reported that the IL-6-174GG-genotype is associated with increased susceptibility to sepsis, and the IL-6-174CC-genotype is more common in preterm infants with severe intraventricular hemorrhage (IVH). We studied 1206 preterm infants with a birth weight below 1500 g. In contrast to previously published data, the frequency of IVH grade IV, periventricular leukomalacia, ventricular-peritoneal-shunting or death was not different between infants with different IL-6-genotypes: IL-6-174GG (n ¼ 430) 8%, IL-6-174GC (n ¼ 605) 9% and IL-6-174CC (n ¼ 167) 12% (P ¼ 0.2 for IL-6-174CC vs GG þ GC). Furthermore, we were not able to confirm previously reported association between sepsis and the IL-6-174GG-genotype. Blood-culture-proven sepsis occurred in 19% of IL-6-174GG-carriers (n ¼ 157), 26% of IL-6-174GC-carriers (n ¼ 193) and 27% of infants carrying the IL-6-174CC-genotype (n ¼ 67). We were not able to confirm previously reported associations between sepsis, cerebral injury and the IL-6-174-genotype in VLBW-infants.

Interleukin-6 (-174C) polymorphism and the risk of sepsis in very low birth weight infants: meta-analysis

“…Five articles that reported six cohort studies fulfilled the review eligibility criteria (table 1). 4 5 7 – 9 Two studies were reported in a single publication 8. Most studies were based in neonatal intensive care settings in Europe where participating infants were mostly of Caucasian ethnic ancestry.…”

“…It was proposed that screening VLBW newborn infants for this polymorphism may allow antimicrobial prophylaxis to be targeted to infants at highest risk of developing sepsis 6. However, subsequent genetic association studies have reported conflicting results 7 – 9…”

Interleukin-6 -174 and -572 Genotypes and the Volume of Deep Gray Matter in Preterm Infants

“…In addition, IL-6 -174 CC genotype was associated with disability at 2 or 5 1 ⁄2 y of age (12). Quite contrary, Göpel et al (13) did not find any association between intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) and IL-6 -174 genotypes. In addition, in the only available study of IL-6 -572 polymorphism, IL-6 -572 C genotype was reported to associate with less optimal neurodevelopmental performance at 2 y of corrected age and at 5 1 ⁄2 y of age in preterm infants (14).…”

Genetic susceptibility to neonatal infection

“…Furthermore, IL-6 polymorphism conferred an increased risk for PTD [46] and further studies suggested that the IL6-174 GG genotype was associated with higher risk for bacterial sepsis in preterm infants [50]. This finding was initially confirmed by another group [51 ] but could not be reproduced by a larger subsequent study from the same group [52,53 ].…”