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Objective: Chorioamnionitis (CAM), an ascending infection from maternal bacterial vaginosis or cervicitis, can cause preterm delivery. We hypothesized that lactoferrin (LF), in particular recombinant human LF (rh-LF), may prevent preterm delivery. We conducted three experiments to demonstrate LF's ability to prevent preterm delivery. Materials and Methods: First, we correlated human cervical mucus LF concentration and LF and interleukin6 (IL-6) concentrations in amniotic fluid to gestational weeks, in mothers with and without CAM. Second, using an amnion cell culture system, we studied the preventive effect of rh-LF on inflammatory cytokine production induced by lipopolysaccharide. Using human cervical gland cell lines, we studied the preventive effects of rh-LF on the growth of Escherichia coil. Thirdly, we studied the preventive effect of rh-LF in mouse and rabbit models of preterm delivery. We also examined LF's preventive effect on the production of inflammatory cytokines in maternal serum and amniotic fluid. Results: In mothers with CAM, amniotic fluid LF concentrations were elevated and IL-6 production increased as fetal LF levels and inflammation increased. LF administration prevented IL-6 production, demonstrating LF's anti-cytokine action and control over E. coil. Length of pregnancy was extended and fetal survival rates were higher in mothers who received LF. Conclusion: It appears that LF is highly beneficial in the prevention of preterm delivery and improving poor fetal prognosis due to elevated inflammatory cytokine levels. Specifically, rh-LF may prevent the production of inflammatory cytokines under E. coil infection or control maternal cytokine production.

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