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Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice

1994; Elsevier BV; Volume: 170; Issue: 5 Linguagem: Inglês

10.1016/s0002-9378(13)90489-0

1097-6868

Paul L. Fidel, Roberto Romero, Norbert A. Wolf, Jessica Cutright, Marcelo Ramírez, Heriberto Araneda, David B. Cotton,

Reproductive System and Pregnancy

OBJECTIVE: Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and arnniotic fluid concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1α. STUDY DESIGN: 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 μg/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1,4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-α, interleukin-6, and interleukin-1α were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 ILg 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-α 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-1α 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-1α was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-α was not significantly increased in amniotic fluid. CONCLUSION: Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1α and in amniotic fluid concentrations of interleukin-6 and interleukin-1α. OBJECTIVE: Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and arnniotic fluid concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1α. STUDY DESIGN: 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 μg/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1,4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-α, interleukin-6, and interleukin-1α were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 ILg 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-α 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-1α 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-1α was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-α was not significantly increased in amniotic fluid. CONCLUSION: Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1α and in amniotic fluid concentrations of interleukin-6 and interleukin-1α.