Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice.
OBJECTIVE
Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha.


METHODS
C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive an intraperitoneal injection of phosphate-buffered saline solution or lipopolysaccharide (50 micrograms/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1, 4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha were determined with sensitive and specific enzyme-linked immunoassays.


RESULTS
The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 micrograms lipopolysaccharide than in phosphate-buffered saline solution-treated mice (median 15.5 hours, range: 10 to 105 hours vs median 88.5 hours, range: 53 to 105 hours; p < 0.001). In comparison with phosphate-buffered saline solution-treated mice, a distinct serum cytokine pattern was observed in lipopolysaccharide-treated mice. Concentrations of tumor necrosis factor-alpha were detectable 1 and 4 hours after lipopolysaccharide injection (median 874 pg/ml, range: < 100 to 8000 pg/ml, p < 0.001; and median 263 pg/ml, range: < 100 to 927 pg/ml, p < 0.001, respectively). Concentrations of interleukin-6 were elevated at 1, 4, and 10 hours (median 11.8 ng/ml, range: 6 to 500 ng/ml, p < 0.001; median 27.1 ng/ml, range: 4.5 to 192 ng/ml, p < 0.001; median 1.95 ng/ml, range: < 0.05 to 35 ng/ml, p < 0.015, respectively). Concentrations of interleukin-1 alpha were significantly increased 4 hours after lipopolysaccharide injection (median 102 pg/ml, range: < 15 to 306 pg/ml, p < 0.001). A cytokine pattern distinct from serum was observed in amniotic fluid of lipopolysaccharide-treated mice. In comparison with controls, concentrations of interleukin-6 were significantly elevated 4 and 10 hours after treatment with lipopolysaccharide (median 0.88 ng/ml, range: 0.40 to 2.7 ng/ml, p < 0.025; and median 4 ng/ml, range: 1.9 to 33.6 ng/ml, p < 0.001, respectively). Interleukin-1 alpha was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-alpha was not significantly increased in amniotic fluid.


CONCLUSIONS
Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha and in amniotic fluid concentrations of interleukin-6 and interleukin-1 alpha.
Fidel
P L
PL
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
Romero
R
R
Wolf
N
N
Cutright
J
J
Ramirez
M
M
Araneda
H
H
Cotton
D B
DB
D000653:Amniotic Fluid / Q000276:immunology / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli; D005260:Female; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism*; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D007752:Obstetric Labor, Premature / Q000209:etiology / Q000276:immunology*; D011247:Pregnancy; D011897:Random Allocation; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha