Pretreatment With Toll-like Receptor 4 Antagonist Inhibits Lipopolysaccharide-Induced Preterm Uterine Contractility, Cytokines, and Prostaglandins in Rhesus Monkeys

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2008-02, Vol.15 (2), p.121-127
• Main Authors: Adams Waldorf, Kristina M., Persing, David, Novy, Miles J., Sadowsky, Drew W., Gravett, Michael G.
• Format: Article
• Language: English
• Subjects: Amniotic Fluid - microbiology; Animals; Chorioamnionitis; Cytokines - immunology; Disease Models, Animal; Embryology; Escherichia coli; Female; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - immunology; Macaca mulatta; Medicine & Public Health; Obstetric Labor, Premature - immunology; Obstetric Labor, Premature - prevention & control; Obstetrics/Perinatology/Midwifery; Pregnancy; Pregnancy Complications, Infectious - immunology; Prostaglandins - immunology; Reproductive Medicine; Toll-Like Receptor 4 - antagonists & inhibitors; Uterine Contraction - drug effects; Uterine Contraction - immunology; Uterine Diseases - microbiology
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719107310992

Intrauterine infection, which occurs in most early preterm births, triggers an immune response culminating in preterm labor. The authors hypothesize that blockade of lipopolysaccharide (LPS)—induced immune responses by a toll-like receptor 4 antagonist (TLR4A) would prevent elevations in amniotic fluid (AF) cytokines, prostaglandins, and uterine contractility. Chronically catheterized rhesus monkeys at 128 to 147 days' gestation received intra-amniotic infusions of either (1) saline (n = 6), (2) LPS (0.15-10 µg; n = 4), or (3) TLR4A pretreatment with LPS (10 µg) 1 hour later (n = 4). AF cytokines, prostaglandins, and uterine contractility were compared using 1-way ANOVA with Bonferroniadjusted pairwise comparisons. Compared with saline controls, LPS induced significant elevations in AF interleukin-8 (IL-8), tumor necrosis factor (TNF)— α, PGE2, PGF2 α , and uterine contractility (P < .05). In contrast, TLR4A pretreatment inhibited LPS-induced uterine activity and was associated with significantly lower AF IL-8, TNF-α, PGE2, and PGF2 α versus LPS alone (P < .05). Toll-like receptor antagonists, together with antibiotics, may delay or prevent infection-associated preterm birth.