Does carbon monoxide inhibit proinflammatory cytokine production by fetal membranes?

Infection-induced inflammation is a common cause of preterm birth. Pharmacologic inhibition of proinflammatory cytokines improves pregnancy outcome in animal models but there are no universally effective therapies for preterm birth in women. Carbon monoxide (CO) has anti-inflammatory properties at low concentrations but its effects on reproductive tissues is unclear. Therefore, we studied the effect of supplemental CO on the production of cytokines associated with preterm birth by fetal membranes.

Cross-sections of whole fetal membranes, isolated choriodecidua, and isolated amnion were prepared using tissues collected from women who had normal vaginal deliveries at term. Tissues were placed in an organ explant culture system and stimulated with up to 10(8) CFU/mL Escherichia coli. Cultures were incubated under room air or room air+250 ppm CO for 18 h and cytokine concentrations in conditioned medium were quantified by ELISA.

CO inhibited IL-1β and TNF-α (P≤0.001) production by cultures stimulated with 10(7) CFU/mL bacteria but had no detectable effect on IL-10 by full-thickness membranes. Although CO also tended to reduce TNF-α production (P=0.053), no effect of CO was detected for IL-10 or IL-1β for membranes stimulated with 10(8) CFU/mL E. coli. TNF-α, but not IL-1β or IL-10 production, was inhibited by CO for choriodecidual cultures stimulated with 10(7) or 10(8) CFU/mL E. coli (P<0.001). IL-1β production was significantly inhibited by CO for amnion cultures stimulated with 10(7) (P=0.002) and 10(8) (P=0.017) CFU/mL E. coli. Exposure to bacteria had no effect on TNF-α or IL-10 production but CO tended to increase IL-10 production by amnion cultures stimulated with 10(8) CFU/mL E. coli (P=0.037).

These results suggest that CO may help promote an anti-inflammatory environment during intrauterine infections by inhibiting TNF-α and IL-1β production.