Profound lack of interleukin (IL)-12/IL-23p40 in neonates born early in gestation is associated with an increased risk of sepsis.

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.

• Authors: Pascal M Lavoie, Qing Huang, Elyse Jolette, Mihoko Whalen, Anne Monique Nuyt, Francois Audibert, David P Speert, Thierry Lacaze-Masmonteil, Hugo Soudeyns, Tobias R Kollmann
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 202 Issue 11 Pg. 1754-63 (Dec 01 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20977341 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-12 Subunit p40
• Toll-Like Receptors
• Interleukin-12

Topics

• British Columbia
• Fetal Blood
• Flow Cytometry
• Humans
• Infant, Newborn
• Infant, Premature
• Infant, Premature, Diseases (immunology)
• Interleukin-12 (blood)
• Interleukin-12 Subunit p40 (blood)
• Risk Factors
• Sepsis (immunology)
• Toll-Like Receptors (blood)