Plasma cytokine profiles in very preterm infants with late-onset sepsis

Abstract

Introduction: Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood.

Aims: To characterise plasma pro- and anti-inflammatory cytokine concentrations and pre-defined ratios in very preterm infants with late-onset sepsis (LOS).

Methods: In this observational study, peripheral blood samples were collected at the time of evaluation for suspected LOS from 31 preterm infants (<30 weeks gestational age). Plasma cytokine concentrations were determined by 12-plex immunoassay.

Results: IL-10, IFN-γ, IL-12p70, IP-10, IL-6 and CCL2 were elevated in the majority infants with LOS (n = 12) compared to those without LOS (n = 19). There was no difference in TNF-α, IL-1β, IL-17AF, IL-8 and IL-15 concentrations between groups. IL-10/TNF-α ratios were increased, while CCL2/IL-10 and IL-12p70/IL-10 ratios were decreased in infants with LOS compared to those without.

Conclusion: Very preterm infants have a marked innate inflammatory response at the time of LOS. The increase in IL-10/TNF-α ratio may indicate early immune hypo-responsiveness. Longitudinal studies with a larger number of participants are required to understand immune responses and clinical outcomes following LOS in preterm infants.

Fig 1. Cytokine ratio at the time of late-onset sepsis evaluation.

Comparison of a) IL-10/TNF-α, b) IP-10/IL-10, c) IL-6/IL-10, d) CCL2/IL-10, e) IL-12p70/IL-10 and f) IFN-γ/IL-10 from infants with confirmed LOS (n = 12 episodes, closed circles) and no LOS (n = 19 episodes, closed triangles). Cytokines were measured by bead-based multiplex assay. All data shown on a log scale with median with 95% confidence intervals. Symbols depict level of significance between confirmed LOS and no LOS groups (*P = 0.048; **P = 0.003; ***P = 0.0002) by Mann-Whitney test. LOS, late-onset sepsis; IL, interleukin; IFN, interferon; IP, inducible protein; CCL2, chemokine (C-C motif) ligand-2.