Maternal lipopolysaccharide-induced inflammation during pregnancy programs impaired offspring innate immune responses.
OBJECTIVE
Because the fetal innate immune system is responsive, while still maturing during the preterm period, we hypothesized that the early activation of fetal inflammatory pathways may have an impact on the ultimate expression of immune competency.


METHODS
Pregnant Sprague Dawley rats (n = 7; Harlan Sprague Dawley Inc, Jerusalem, Israel) at 18 days gestation received intraperitoneal injections of saline solution or lipopolysaccharides (500 microg/kg). Pups were delivered spontaneously. At postnatal day 24, pups received intraperitoneal lipopolysaccharide (100 microg/kg), and plasma cytokine levels were measured before and 4 hours after lipopolysaccharide administration.


RESULTS
In response to lipopolysaccharides, pups of the lipopolysaccharide-injected dams had significantly (P < .05) reduced interleukin-6 (median [25th,75th percentile], 229 [84,6086] vs 4745 [2765,6643] pg/mL), interleukin-1beta (median [25th,75th percentile], 820 [125,1196] vs 1682 [1515,2127] pg/mL), tumor necrosis factor-alpha (median [25th,75th percentile], 4.8 [1.2,91] vs 163 [46,205] pg/mL), and interleukin-10 responses, when compared with saline solution-injected dams.


CONCLUSIONS
Maternal lipopolysaccharide exposure suppresses offspring innate immune response to inflammatory stimuli. These results suggest that maternal inflammatory exposures during pregnancy may impair newborn infant innate responses and increase susceptibility to infection.
Beloosesky
Ron
R
Department of Obstetrics/Gynecology, Rambam Medical Center, Haifa, Israel. tomor2304@yahoo.com
Maravi
Nir
N
Weiner
Zeev
Z
Khatib
Nizar
N
Awad
Nibal
N
Boles
Julie
J
Ross
Michael G
MG
Itskovitz-Eldor
Joseph
J
D000818:Animals; D000831:Animals, Newborn; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D007274:Injections, Intraperitoneal; D007378:Interleukins / Q000378:metabolism*; D008070:Lipopolysaccharides; D018811:Maternal Exposure; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D007378:Interleukins; D008070:Lipopolysaccharides