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Indomethacin blocks interleukin 1β–induced myometrial contractions in pregnant rhesus monkeys

Indomethacin blocks interleukin 1β–induced myometrial contractions in pregnant rhesus monkeys Objective: We sought to determine whether blockade of prostaglandin synthesis with indomethacin prevents interleukin 1β–induced increases in uterine contractions in a nonhuman primate model. Study Design: Maternal and fetal vascular catheters, intra-amniotic fluid pressure catheters, and fetal electrocardiographic and myometrial electromyographic electrodes were implanted in 11 rhesus monkeys at 124 ± 2 days’ gestation (term, 167 days). After postsurgical stabilization (136 ± 2 days) indomethacin 50 mg was administered orally twice daily for 5 days (n = 6). On day 3 human recombinant interleukin 1β 10 μg was infused into the amniotic cavity over 2 hours. Five days after the last indomethacin dose the study was repeated without indomethacin treatment. Uterine activity was continuously monitored and quantified as the hourly contraction area (millimeters of mercury · seconds per hour) in the experimental group and a control group (n = 5) that received interleukin 1β alone. At timed intervals amniotic fluid was sampled for leukocyte counts and assayed for prostaglandin E and F, the inflammatory cytokines interleukin 1β, interleukin 6, interleukin 8, tumor necrosis factor α, and interleukin 1 receptor antagonist by specific assays. Results: Uterine activity was increased severalfold from baseline after interleukin 1β infusion alone and in the absence of indomethacin treatment ( P < .05). There was no increase in uterine contractility when interleukin 1β was infused concurrently with indomethacin treatment. Concentrations of amniotic fluid leukocytes and cytokines increased significantly after interleukin 1β infusion in both the presence and absence of indomethacin. Amniotic fluid prostaglandins E and F were suppressed during indomethacin treatment but rose significantly after interleukin 1β infusion in the absence of indomethacin. Except for higher interleukin 6, cytokine levels were unaltered by indomethacin. Conclusions: After interleukin 1β infusion, indomethacin blocked the development of uterine activity. Amniotic fluid prostaglandins were suppressed by indomethacin treatment, but cytokines and leukocytes were not. These results suggest that prostaglandins or possibly other indomethacin-suppressible compounds stimulate uterine activity after interleukin 1β infusion in late-gestation rhesus monkeys or that indomethacin has direct tocolytic effects. (Am J Obstet Gynecol 2000;183:173-80.) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Obstetrics and Gynecology Wolters Kluwer Health

Indomethacin blocks interleukin 1β–induced myometrial contractions in pregnant rhesus monkeys

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2000 Academic Press
ISSN
0002-9378
DOI
10.1067/mob.2000.105968
pmid
10920327
Publisher site
See Article on Publisher Site

Abstract

Objective: We sought to determine whether blockade of prostaglandin synthesis with indomethacin prevents interleukin 1β–induced increases in uterine contractions in a nonhuman primate model. Study Design: Maternal and fetal vascular catheters, intra-amniotic fluid pressure catheters, and fetal electrocardiographic and myometrial electromyographic electrodes were implanted in 11 rhesus monkeys at 124 ± 2 days’ gestation (term, 167 days). After postsurgical stabilization (136 ± 2 days) indomethacin 50 mg was administered orally twice daily for 5 days (n = 6). On day 3 human recombinant interleukin 1β 10 μg was infused into the amniotic cavity over 2 hours. Five days after the last indomethacin dose the study was repeated without indomethacin treatment. Uterine activity was continuously monitored and quantified as the hourly contraction area (millimeters of mercury · seconds per hour) in the experimental group and a control group (n = 5) that received interleukin 1β alone. At timed intervals amniotic fluid was sampled for leukocyte counts and assayed for prostaglandin E and F, the inflammatory cytokines interleukin 1β, interleukin 6, interleukin 8, tumor necrosis factor α, and interleukin 1 receptor antagonist by specific assays. Results: Uterine activity was increased severalfold from baseline after interleukin 1β infusion alone and in the absence of indomethacin treatment ( P < .05). There was no increase in uterine contractility when interleukin 1β was infused concurrently with indomethacin treatment. Concentrations of amniotic fluid leukocytes and cytokines increased significantly after interleukin 1β infusion in both the presence and absence of indomethacin. Amniotic fluid prostaglandins E and F were suppressed during indomethacin treatment but rose significantly after interleukin 1β infusion in the absence of indomethacin. Except for higher interleukin 6, cytokine levels were unaltered by indomethacin. Conclusions: After interleukin 1β infusion, indomethacin blocked the development of uterine activity. Amniotic fluid prostaglandins were suppressed by indomethacin treatment, but cytokines and leukocytes were not. These results suggest that prostaglandins or possibly other indomethacin-suppressible compounds stimulate uterine activity after interleukin 1β infusion in late-gestation rhesus monkeys or that indomethacin has direct tocolytic effects. (Am J Obstet Gynecol 2000;183:173-80.)

Journal

American Journal of Obstetrics and Gynecology – Wolters Kluwer Health

Published: Jul 1, 2000

References

  • New perspectives on the prevention of extreme prematurity
    Novy, MJ; McGregor, JA; Iams, JD
  • Infection, inflammation, and contractions: the role of cytokines in the pathophysiology of preterm labor
    Dudley, DJ; Trautman, MS
  • The natural interleukin-1 receptor antagonist prevents interleukin-1 induced preterm delivery in mice
    Romero, R; Tartakovsky, B
  • Interleukin-6 stimulates prostaglandin production by human amnion and decidual cells
    Mitchell, MD; Dudley, DJ; Edwin, SS
  • An experimental model for intraamniotic infection and preterm labor in rhesus monkeys
    Gravett, MG; Witkin, SS; Haluska, GJ; Edwards, JL; Cook, MJ; Novy, MJ
  • Interleukin-1β intraamniotic infusion induces tumor necrosis factor-α, prostaglandin production, and preterm contractions in pregnant rhesus monkeys
    Baggia, S; Gravett, MG; Witkin, SS; Haluska, GJ; Novy, MJ
  • Efficacy and safety of indomethacin versus ritrodrine in the management of preterm labor: a randomized study
    Morales, WJ; Smith, SG; Angel, JL; O’Brien, WF; Knuppel, RA
  • Inflammatory cytokine (interleukins 1, 6, and 8 and tumor necrosis factor-α) release from cultured human fetal membranes in response to endotoxic lipopolysaccharide mirrors amniotic fluid concentrations
    Fortunato, SJ; Menon, RP; Swan, KF; Menon, R
  • Immunologic aspects of preterm labor
    Mitchell, MD; Branch, DW; Schiller, S; Romero, RJ; Daynes, RA; Dudley, DJ
  • Interleukin-8 release from human gestational tissue explants: effects of gestation, labor, and chorioamnionitis
    Laham, N; Brennecke, SP; Rice, GE
  • Transfer of cytokines through human fetal membranes
    Kent, ASH; Sullivan, MHF; Elder, MG
  • Amniotic fluid prolactin is decreased by experimental intrauterine infection of IL-1β infusion but not via prostaglandins in pregnant rhesus macaques
    Bethea, CL; Gravett, MG; Sadowsky, DW; Haluska, GJ; Axthelm, MK; Novy, MJ
  • Mechanism of interleukin-1β stimulation of human amnion prostaglandin biosynthesis: mediation via a novel inducible cyclooxygenase
    Mitchell, MD; Edwin, SS; Schiller, S; Silver, RM; Smotkin, D; Trautman, MS
  • Tumor necrosis factor-alpha promotes sustained cyclooxygenase-2 expression: attenuation by dexamethasone and NSAIDs
    Perkins, DJ; Kniss, DA
  • Interleukin-1 and tumor necrosis factor stimulate arachidonic acid release and phospholipid metabolism in human myometrial cells
    Molnar, M; Romero, R; Hertelendy, F
  • Prostaglandin dehydrogenase and the iniation of labor
    Challis, JRG; Patel, FA; Pomini, F
  • Degenerative changes and detection of plasminogen in fetal membranes that rupture prematurely
    Jenkins, DM; O’Neill, M; Mattar, M; France, VM; Hsi, B; Faulk, WP
  • 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor
    Ortega, F; Avila, G; Furth, E; Lei, H; Muschel, R; Stevenson, W
  • Poly’s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response
    Lloyd, AR; Oppenheim, JJ
  • Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators
    Pugin, J; Widmer, MC; Kossodo, S; Liang, CM; Preas, HL; Suffredini, AF
  • The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology
    Romero, R; Salafia, CM; Athanassiadis, AP; Hanaoka, S; Mazor, M; Sepulveda, W
  • Fetal origin of amniotic fluid polymorphonuclear leukocytes
    Sampson, JE; Theve, RP; Blatman, RN; Shipp, TD; Bianchi, DW; Ward, BE
  • Human polymorphonuclear leukocytes derived from chronically inflamed tissue express inflammatory cytokines in vivo
    Takeichi, O; Saito, I; Tsurumachi, T; Saito, T; Moro, I
  • Role of prostaglandins, prostacyclin, and thromboxanes in the physiologic control of the uterus and in parturition
    Novy, MJ; Liggins, GC
  • Indomethacin attenuates oxytocin and hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1 beta
    Buller, KM; Xu, Y; Day, TA
  • Arachidonate lipoxygenase metabolites in amniotic fluid of women with intraamniotic infection and preterm labor
    Romero, R; Quintero, R; Emamian, M; Wan, M; Grzyboski, C; Hobbins, JC
  • 5-Hydroxyeicosatetraenoic acid biosynthesis by gestational tissues: Effects of inflammatory cytokines
    Edwin, SS; LaMarche, SL; Thai, D; Branch, DW; Mitchell, MD
  • Aspirin-like drugs interfere with arachidonate metabolism by inhibition of the 12-hydroperoxy-5, 8, 10, 14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway
    Siegel, MI; McConnell, RT; Cuatrecasas, P
  • Effect of indomethacin on cyclic AMP phosphodiesterase activity in myometrium from pregnant rhesus monkeys
    Beatty, DH; Bocek, RM; Young, MK; Novy, MJ
  • Effect of nimesulide and indomethacin on contractility and the Ca 2+ channel current in myometrial smooth muscle from pregnant women
    Sawdy, R; Knock, GA; Bennett, PR; Poston, L; Aaronson, PI
  • Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep
    Poore, KR; Young, IR; Hirst, JJ
  • Shirodkar cerclage in a multifactorial approach to the patient with advanced cervical changes
    Novy, MJ; Haymond, J; Nichols, M