Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model

Michael G. Gravett, Kristina M. Adams, Drew W. Sadowsky, Alexandra R. Grosvenor, Steven S. Witkin, Michael Axthelm, Miles J. Novy

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    Objective: The purpose of this study was to determine whether treatment with ampicillin together with dexamethasone and indomethacin delays preterm birth that is induced by intraamniotic group B Streptococcus in a nonhuman primate model. Study Design: After contraction onset that was induced by group B Streptococcus (106 colony-forming units/mL), chronically instrumented rhesus macaques received either no treatment (controls; n = 6); ampicillin (n = 4); or ampicillin + dexamethasone + indomethacin (n = 5). Outcomes included the interval from contraction onset until delivery and concentrations of amniotic fluid inflammatory mediators. Results: Mean interval from contraction onset until delivery was 33 ± 8.7 hours in controls, 82 ± 28.0 hours with ampicillin (P = .18, vs controls), and 213 ± 50.8 hours with ampicillin + dexamethasone + indomethacin (P = .004, vs controls). Ampicillin eradicated group B Streptococcus; however, uterine activity, amniotic fluid cytokines, prostaglandins, and matrix metalloproteinase-9 remained elevated. Ampicillin + dexamethasone + indomethacin suppressed interleukin-1β, tumor necrosis factor-α, and prostaglandins E2 and F but did not alter matrix metalloproteinase expression or chorioamnionitis. Conclusion: The combination of ampicillin + dexamethasone + indomethacin suppressed inflammation and significantly prolonged gestation.

    Original languageEnglish (US)
    JournalAmerican Journal of Obstetrics and Gynecology
    Volume197
    Issue number5
    DOIs
    StatePublished - Nov 2007

    Fingerprint

    Immunologic Factors
    Ampicillin
    Primates
    Anti-Bacterial Agents
    Indomethacin
    Dexamethasone
    Infection
    Streptococcus agalactiae
    Amniotic Fluid
    Chorioamnionitis
    Dinoprost
    Matrix Metalloproteinase 9
    Premature Birth
    Macaca mulatta
    Matrix Metalloproteinases
    Interleukin-1
    Dinoprostone
    Prostaglandins
    Stem Cells
    Tumor Necrosis Factor-alpha

    Keywords

    • cytokine
    • intraamniotic infection
    • preterm labor
    • prostaglandins
    • rhesus macaque

    ASJC Scopus subject areas

    • Medicine(all)
    • Obstetrics and Gynecology

    Cite this

    Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model. / Gravett, Michael G.; Adams, Kristina M.; Sadowsky, Drew W.; Grosvenor, Alexandra R.; Witkin, Steven S.; Axthelm, Michael; Novy, Miles J.

    In: American Journal of Obstetrics and Gynecology, Vol. 197, No. 5, 11.2007.

    Research output: Contribution to journalArticle

    Gravett, Michael G. ; Adams, Kristina M. ; Sadowsky, Drew W. ; Grosvenor, Alexandra R. ; Witkin, Steven S. ; Axthelm, Michael ; Novy, Miles J. / Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model. In: American Journal of Obstetrics and Gynecology. 2007 ; Vol. 197, No. 5.
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    AB - Objective: The purpose of this study was to determine whether treatment with ampicillin together with dexamethasone and indomethacin delays preterm birth that is induced by intraamniotic group B Streptococcus in a nonhuman primate model. Study Design: After contraction onset that was induced by group B Streptococcus (106 colony-forming units/mL), chronically instrumented rhesus macaques received either no treatment (controls; n = 6); ampicillin (n = 4); or ampicillin + dexamethasone + indomethacin (n = 5). Outcomes included the interval from contraction onset until delivery and concentrations of amniotic fluid inflammatory mediators. Results: Mean interval from contraction onset until delivery was 33 ± 8.7 hours in controls, 82 ± 28.0 hours with ampicillin (P = .18, vs controls), and 213 ± 50.8 hours with ampicillin + dexamethasone + indomethacin (P = .004, vs controls). Ampicillin eradicated group B Streptococcus; however, uterine activity, amniotic fluid cytokines, prostaglandins, and matrix metalloproteinase-9 remained elevated. Ampicillin + dexamethasone + indomethacin suppressed interleukin-1β, tumor necrosis factor-α, and prostaglandins E2 and F2α but did not alter matrix metalloproteinase expression or chorioamnionitis. Conclusion: The combination of ampicillin + dexamethasone + indomethacin suppressed inflammation and significantly prolonged gestation.

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