Profound Lack of Interleukin (IL)–12/IL‐23p40 in Neonates Born Early in Gestation Is Associated with an Increased Risk of Sepsis

  • Lavoie P
  • Huang Q
  • Jolette E
 et al. 
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Abstract

BACKGROUND: Infants born prematurely are highly vulnerable to infections and also exhibit a high susceptibility to organ damage due to inflammation.

METHODS: To investigate homeostatic immune control early in life, we used advanced multiparameter flow cytometry to compare responses to multiple Toll-like receptor (TLR) ligands in single cells and mononuclear cell populations in term neonates versus preterm neonates born before 29 weeks of gestation.

RESULTS: Preterm neonates had globally attenuated TLR-stimulated interleukin (IL)-6, interferon-α, and, to a lesser extent, tumor necrosis factor-α responses but demonstrated relative preservation of anti-inflammatory IL-10 responses in monocytes and dendritic cell subtypes. Remarkably, preterm neonates were also profoundly deficient in the common IL-12 and IL-23 cytokines' p40 subunit, which is critical for immunity against a wide variety of microbial pathogens in mice. Consistent with the increased susceptibility to infections resulting from the lack of IL-12/IL-23 in human newborns, significantly lower serum p40 concentrations were observed at birth in infants who developed early-onset sepsis.

CONCLUSION: To our knowledge, this study is the first detailed analysis of multiple TLR function in neonates born extremely premature. Although attenuation of proinflammatory pathways may protect against tissue-damaging immunity early in life, this previously unrecognized p40 immune deficiency appears to result in considerably increased susceptibility to infection in human preterm newborns.

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Authors

  • Pascal M. Lavoie

  • Qing Huang

  • Elyse Jolette

  • Mihoko Whalen

  • Anne Monique Nuyt

  • Francois Audibert

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