OBJECTIVE: To describe the temporal and quantitative consequences of intra-amniotic interleukin-1 beta infusion in a nonhuman primate model. METHODS: On days 128-138 of gestation (term 167 days), four chronically instrumented rhesus monkeys (Macaca mulatta) underwent serial intra-amniotic infusions of 2, 5, and 10-20 micrograms recombinant human interleukin-1 beta. Each infusion was for 2 hours, and subsequent infusions were at least 48 hours later. Amniotic fluid was sampled serially both before and after infusion for interleukin-1 beta, tumor necrosis factor-alpha (TFN-alpha), and prostaglandin (PG) E2 and F2 alpha by specific assays, and uterine activity in each monkey was recorded continuously. RESULTS: Intra-amniotic concentrations of interleukin-1 beta rose dramatically after infusion. This rise was rapidly followed by the appearance of TNF-alpha in the amniotic cavities of all animals, with maximal levels reached 5 hours after the initiation of the infusion. Both interleukin-1 beta and TNF-alpha were rapidly cleared from the amniotic fluid and returned to baseline levels by 24-48 hours. Increases in PGE2 and F2 alpha paralleled those of the two cytokines but remained elevated for the duration of the experiments. The stimulation of uterine contractility from a pre-infusion level of 200 mmHg. seconds/hour to 6000 mmHg. seconds/hour occurred an average of 6-10 hours after interleukin-1 beta infusion. These stimulations were transient, usually abating by 22 hours after infusion, and did not result in frank labor. CONCLUSION: In the rhesus monkey, intra-amniotic infusion of interleukin-1 beta rapidly induces production of intra-amniotic TNF-alpha as well as PGE2 and F2 alpha, followed by uterine contractility. Uterine activity diminishes as cytokine levels return to pre-infusion levels, even in the presence of elevated intraamniotic PG levels. Tumor necrosis factor-alpha may act synergistically with interleukin-1 beta in the pathophysiology of cytokine-related preterm labor.
OBJECTIVE: To describe the temporal and quantitative consequences of intra-amnioticinterleukin-1 beta infusion in a nonhuman primate model. METHODS: On days 128-138 of gestation (term 167 days), four chronically instrumented rhesus monkeys (Macaca mulatta) underwent serial intra-amniotic infusions of 2, 5, and 10-20 micrograms recombinant humaninterleukin-1 beta. Each infusion was for 2 hours, and subsequent infusions were at least 48 hours later. Amniotic fluid was sampled serially both before and after infusion for interleukin-1 beta, tumor necrosis factor-alpha (TFN-alpha), and prostaglandin (PG) E2 and F2 alpha by specific assays, and uterine activity in each monkey was recorded continuously. RESULTS:Intra-amniotic concentrations of interleukin-1 beta rose dramatically after infusion. This rise was rapidly followed by the appearance of TNF-alpha in the amniotic cavities of all animals, with maximal levels reached 5 hours after the initiation of the infusion. Both interleukin-1 beta and TNF-alpha were rapidly cleared from the amniotic fluid and returned to baseline levels by 24-48 hours. Increases in PGE2 and F2 alpha paralleled those of the two cytokines but remained elevated for the duration of the experiments. The stimulation of uterine contractility from a pre-infusion level of 200 mmHg. seconds/hour to 6000 mmHg. seconds/hour occurred an average of 6-10 hours after interleukin-1 beta infusion. These stimulations were transient, usually abating by 22 hours after infusion, and did not result in frank labor. CONCLUSION: In the rhesus monkey, intra-amniotic infusion of interleukin-1 beta rapidly induces production of intra-amnioticTNF-alpha as well as PGE2 and F2 alpha, followed by uterine contractility. Uterine activity diminishes as cytokine levels return to pre-infusion levels, even in the presence of elevated intraamniotic PG levels. Tumor necrosis factor-alpha may act synergistically with interleukin-1 beta in the pathophysiology of cytokine-related preterm labor.
Authors: Pooja Mittal; Roberto Romero; Adi L Tarca; Juan Gonzalez; Sorin Draghici; Yi Xu; Zhong Dong; Chia-Ling Nhan-Chang; Tinnakorn Chaiworapongsa; Stephen Lye; Juan Pedro Kusanovic; Leonard Lipovich; Shali Mazaki-Tovi; Sonia S Hassan; Sam Mesiano; Chong Jai Kim Journal: J Perinat Med Date: 2010-07-14 Impact factor: 1.901
Authors: K Motomura; R Romero; V Garcia-Flores; Y Leng; Y Xu; J Galaz; R Slutsky; D Levenson; N Gomez-Lopez Journal: Mol Hum Reprod Date: 2020-09-01 Impact factor: 4.025
Authors: Heather A Frey; Molly J Stout; Laurel N Pearson; Methodius G Tuuli; Alison G Cahill; Jerome F Strauss; Luis M Gomez; Samuel Parry; Jenifer E Allsworth; George A Macones Journal: Am J Obstet Gynecol Date: 2016-03-12 Impact factor: 8.661