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

Background: Genetic 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. Methods: Infectious 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). Results: The 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). Conclusion: The 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.