Resveratrol Protects Against Pathological Preterm Birth by Suppression of Macrophage-Mediated Inflammation

Reprod Sci. 2015 Dec;22(12):1561-8. doi: 10.1177/1933719115589413. Epub 2015 Jun 2.

Abstract

Inflammatory cytokines play a major role in spontaneous preterm birth. Resveratrol has strong anti-inflammatory effects, but its effect on preterm birth in vivo is unknown. We investigated whether resveratrol protects against preterm birth in the lipopolysaccharide (LPS)-induced preterm mouse model. Twelve-day-old pregnant mice were fed 20 to 40 mg/kg resveratrol daily. On day 15, 10 μg of LPS was injected into uterine cervices. Resveratrol administration significantly decreased the rate of preterm birth. Resveratrol administration abolished LPS-induced elevation of tumor necrosis factor α (TNF-α) and interleukin (IL) 1β but not IL-6 levels. The TNF-α messenger RNA levels were decreased in the cervices of resveratrol-administered mice compared with controls. Resveratrol treatment suppressed the elevation in TNF-α and IL-1β levels in LPS-exposed peritoneal macrophages. Further resveratrol treatment eradicated the proinflammatory cytokine-mediated elevation in cyclooxygenase 2 (COX-2) in peritoneal macrophages. Resveratrol may protect against pathological preterm birth by suppression of elevated proinflammatory cytokines and consequent elevation of COX-2 in macrophages.

Keywords: COX-2; LPS-induced preterm birth; anti-inflammatory effect; peritoneal macrophage; resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Female
  • Gestational Age
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Mice, Inbred C57BL
  • Pregnancy
  • Premature Birth / chemically induced
  • Premature Birth / metabolism
  • Premature Birth / pathology
  • Premature Birth / prevention & control*
  • Resveratrol
  • Stilbenes / pharmacology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, mouse
  • Inflammation Mediators
  • Interleukin-1beta
  • Lipopolysaccharides
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, E coli O55-B5
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Resveratrol