Effect of Carbon Monoxide on Bacteria-Stimulated Cytokine Production by Placental Explants

Problem: Preterm birth is frequently caused by an inflammatory response to ascending infections of the reproductive tract. Carbon monoxide (CO) has potent anti-inflammatory properties at subtoxic concentrations. Whether or not CO can modulate inflammatory responses by placental tissues is unclear. Methods: Placental explant cultures were incubated with heat-killed Escherichia coli or Ureaplasma parvum in the presence or absence of 250 ppm CO for 24 hr. Concentrations of cytokines relative viability of the cultures were quantified. Results: Escherichia coli- and U. parvum-stimulated IL-1β production was significantly inhibited by CO supplementation. Escherichia coli-stimulated, but not U. parvum-stimulated, IFN-γ production was inhibited by CO. While CO inhibited PGE₂ production by unstimulated cells, no effects on bacteria-stimulated prostaglandin production were detected. CO had no effect on basal or E. coli-stimulated TNF-α production but enhanced TNF-α production by cultures stimulated with U. parvum. In addition, CO tended to improve the viability of the placental cultures. Conclusions: Low concentrations of CO tended to reduce proinflammatory cytokines and to promote the production of anti-inflammatory cytokines in a pathogen-specific manner. These properties suggest that CO may be useful for promoting a pro-pregnancy cytokine milieu by placental explants and may reduce the consequences of intrauterine infections.