title: The immunomodulatory and anti-apoptotic effect of dexamethasone in imminent preterm labor: an experimental study.
abstract: The study was designed to investigate the effect of dexamethasone (DEX) on the latency period to delivery in a murine model of preterm labor. To this purpose, pregnant mice were randomly assigned in groups: the control group received water for injection (n=20), the preterm labor group was injected with lipopolysaccharide (LPS) (n=22), while the glucocorticoids group was administered DEX either 1h before (n=17) or after (n=7) lipopolysaccharide. In a first set of experiments animals were monitored to record perinatal outcomes. In another set of experiments, the remaining animals were sacrificed eight h after interventions. Fetuses were homogenized to measure tumor necrosis alpha in supernatants. Maternal splenocytes were isolated and stimulated for cytokine production. Serum of mice was incubated with donor cells from healthy pregnant and non-pregnant animals to induce apoptosis. LPS induced preterm labor but treatment or pretreatment with DEX delayed parturition exerting a favorable impact on survival of delivered fetuses. DEX inverted the increase of fetoplacental tumor necrosis alpha levels. Serum of LPS-stimulated mice induced apoptosis of splenocytes of either pregnant or non-pregnant healthy mice; this was reversed after incubation of splenocytes with serum coming from DEX pre-treated mice. The presented findings suggest that DEX administered either as pre-treatment or treatment prolonged gestation and promoted neonatal survival in a sterile murine model of preterm labor. These favorable outcomes were closely linked to alterations in both immune and apoptotic responses of animals.
authors.affiliation: 3rd Department of Obstetrics and Gynecology, Attikon University Hospital, 12462 Athens, Greece. Electronic address: soma20med@hotmail.com.
authors.forename: Sofia F
authors.initials: SF
authors.lastname: Makrydima
authors.affiliation: 4th Department of Internal Medicine, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Aikaterini C
authors.initials: AC
authors.lastname: Pistiki
authors.affiliation: 3rd Department of Obstetrics and Gynecology, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Charalampos G
authors.initials: CG
authors.lastname: Chrelias
authors.affiliation: 3rd Department of Obstetrics and Gynecology, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Vasileios D
authors.initials: VD
authors.lastname: Sioulas
authors.affiliation: 3rd Department of Obstetrics and Gynecology, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Charalampos S
authors.initials: CS
authors.lastname: Siristatidis
authors.affiliation: Center for Sepsis Control and Care, Jena University Hospital, 07747 Jena, Germany; 4th Department of Internal Medicine, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.affiliation: 3rd Department of Obstetrics and Gynecology, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Demetrios P
authors.initials: DP
authors.lastname: Kassanos
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D007752:Obstetric Labor, Premature / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D003907:Dexamethasone
keywords: Apoptosis; Curdian-zymosan (PubChem CID: 11375554); Dexamethasone; Dexamethasone (PubChem CID: 5743); Endotoxin Lipopolysaccharide (PubChem CID: 53481793); Fluorescein-5-isothiocyanate (PubChem CID: 18730); Immune system; Murine model; Phytohemagglutinin N-glucan (PubChem CID: 45480564); Preterm labor (PTL); Propidium iodide (PubChem CID: 104981)