Format

Send to

Choose Destination
J Infect Dis. 2010 Dec 1;202(11):1754-63. doi: 10.1086/657143. Epub 2010 Oct 26.

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

Author information

1
Child & Family Research Institute, Vancouver, British Columbia, Canada. plavoie@cw.bc.ca

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.

PMID:
20977341
PMCID:
PMC2975517
DOI:
10.1086/657143
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center