Abstract
Preterm birth accounts for the majority of perinatal mortality worldwide and there remains no FDA-approved drug to prevent it. Recently, we discovered that the common drug excipient, N,N-dimethylacetamide (DMA), prevents inflammation–induced preterm birth in mice by inhibiting NF-κB. Since we reported this finding it has come to light that a group of widely used, structurally related aprotic solvents, including DMA, N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF), have anti-inflammatory efficacy. We show here that DMF suppresses LPS-induced TNFα secretion from RAW 264.7 cells and IL-6 and IL-8 secretion from HTR-8 cells at concentrations that do not significantly affect cell viability. In vivo, DMF decreases LPS-induced inflammatory cell infiltration and expression of TNFα and IL-6 in the placental labyrinth, all to near baseline levels. Finally, DMF decreases the rate of preterm birth in LPS-induced pregnant mice (P<.0001) and the rate at which pups are spontaneously aborted (P<.0001). In summary, DMF, a widely used solvent structurally related to DMA and NMP, prevents LPS-induced preterm birth in a murine model without overt toxic or teratogenic effects. Re-purposing the DMA/DMF/NMP family of small molecules as anti-inflammatory drugs is a promising new approach to preventing inflammation–induced preterm birth and potentially other inflammatory disorders as well.
Maternal obesity impacts fetal neuroinflammation in a murine model of preterm birth
