IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants

Abstract

BackgroundGenetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection.MethodsInfectious complications were retrospectively determined in 293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single nucleotide polymorphisms (SNPs).ResultsThe IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI) in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI: 1.1–6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of 40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and 63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%) compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04–4.19, p = 0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003).ConclusionThe IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.

Host Genetics and Pediatric Sepsis

“…The -174 G allele associated with low levels of IL-6 appears to be associated with sepsis in Caucasian premature neonates [143,144] while in an African-American cohort, it is the C allele that demonstrates this association [145]. Furthermore, a recent meta-analysis suggests that the IL-6 -174 polymorphism is not strongly associated with the risk of sepsis in this age group [146].…”

“…The association with lower mortality is independent of age and APACHE II score at admission [265]. The association with reduced mortality may be related to the increased fibrinogen A2 allele associated with variable levels of IL-1RA; A2 associated with increased risk of in adults but not children with sepsis; A2 associated with increased mortality in adults with sepsis; +2018 "2 allele" associated with increased mortality in children with meningococcal disease and more severe lung disease in children with pneumonia [120,122,[125][126][127][128] IL-6 -174 G/C G associated with increased IL-6 levels in adult patients but decreased levels in neonates; C associated with increased levels in monocytes from neonates, sepsis in neonates, and severe sepsis and organ dysfunction in children [130,[142][143][144][145][146]281] levels among patients with the GAA haplotype since the 455 A allele within the haplotype is associated with increased transcription. Another polymorphism in the fibrinogen gene, the Val34Leu polymorphism is known to alter the fibrin meshwork with variable permeation characteristics.…”

Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective

“…Aydemir et al 21 Härtel et al 9 Abu-Maziad et al 22 Auriti et al 23 Koroglu et al 24 Spiegler et al 25 Abdel-Hady et al 26 Bertalan et al 27 Reiman et al 28 Dzwonek et al 29 van Der Zwet et al 30 Schueller et al 31 Derzbach et al 32 Härtel et al 33 Baier et al 34 Göpel et al…”

“…In at least one well-controlled study, 34 ethnicity played a major role in modifying associations between polymorphisms in immunologically relevant genes (IL-6 and CD14) and sepsis-related outcomes.…”

“…36 The complexity is highest in the case of MBL, 34 given allele in the TNF-alpha system results in significantly reduced transcription rates and decreased protein release was achieved in a non-physiological ex vivo assay. 51 While it is possible that this reflects physiological potential in the context of sepsis, the latter is much more difficult to ascertain.…”