Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery.
OBJECTIVE
The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery.


METHODS
Wild type or interleukin (IL)-10(-/-) mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells.


RESULTS
Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10(-/-), but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10(-/-) mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-alpha neutralization in these mice restored term delivery. Furthermore, TNF-alpha neutralization prevented uNK cell infiltration and placental cell apoptosis.


CONCLUSIONS
The uNK cell-TNF-alpha-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.
Murphy
Shaun P
SP
Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, RI, USA.
Hanna
Nazeeh N
NN
Fast
Loren D
LD
Shaw
Sunil K
SK
Berg
Göran
G
Padbury
James F
JF
Romero
Roberto
R
Sharma
Surendra
S
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005865:Gestational Age; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D007752:Obstetric Labor, Premature / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D010920:Placenta / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014599:Uterus / Q000166:cytology / Q000276:immunology*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10