N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth

Am J Pathol. 2013 Aug;183(2):422-30. doi: 10.1016/j.ajpath.2013.05.006. Epub 2013 Jun 12.


The proinflammatory response leads to various types of pathologic pathways, including the development of preterm birth. Preterm birth occurs in 12% of deliveries in the United States and causes more than 70% of perinatal morbidity and mortality. The most common cause of spontaneous preterm birth is intrauterine infection in the mother. There is accumulating evidence indicating that the release of proinflammatory cytokines plays a critical role in the pathogenesis of inflammation-associated premature delivery. We found that the common organic solvent, N,N-dimethylacetamide (DMA), prevents endotoxin-induced preterm birth in timed pregnant C57BL/6 embryonic day (E)15.5 mice and rescues their pups from spontaneous abortion at doses many-fold lower than those currently used clinically and in a dose-dependent fashion. We also provide histologic evidence that DMA suppresses the endotoxin-triggered proinflammatory response by significantly attenuating inflammatory cell infiltration of placental tissue. Furthermore, immunoblotting analysis of placental tissue harvested from our murine models revealed DMA-mediated regulation of expression of the proinflammatory cytokines IL-1β, tumor necrosis factor α, and IL-6, and increased expression of the regulatory inflammatory cytokine IL-10. By using in vitro studies, we provide evidence that DMA suppresses macrophage function and that this small molecule prevents nuclear translocation of nuclear factor-kB. These results suggest that DMA represents a newly discovered, nontoxic therapy for a broad range of inflammatory disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetamides / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / drug effects*
  • Endotoxins / toxicity*
  • Female
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / drug effects
  • Pregnancy
  • Premature Birth / chemically induced
  • Premature Birth / prevention & control*


  • Acetamides
  • Anti-Inflammatory Agents
  • Cytokines
  • Endotoxins
  • Lipopolysaccharides
  • NF-kappa B
  • dimethylacetamide