Preventive effect of recombinant human lactoferrin on lipopolysaccharide-induced preterm delivery in mice.

Background: In order to investigate whether recombinant human lactoferrin (rh-LF) has the same effect as bovine LF (b-LF) for the prevention of preterm delivery, we conducted the following animal studies.

Methods: Female C3H/HeNCrj mice were pair-mated with male Crj:B6D2F1 mice. As a model of preterm delivery, on day 15 of gestation, a 50 microg/kg intraperitoneal injection of lipopolysaccharide (LPS) was administered twice with a 3-hr interval between injections (14:00 and 17:00 hours). At 1 hr prior to each LPS injection (13:00 and 16:00 hours), an intraperitoneal injection of saline, b-LF, or rh-LF (1 mg/body) was administered. In non-LPS-treated controls, an intraperitoneal injection of saline was administered four times (13:00, 14:00, 16:00, and 17:00 hours). We measured body weight and recorded delivery time. To measure plasma levels of interleukin-6 (IL-6), other pregnant mice, in which the same preparation as mentioned above had been done, were killed 6 h after the second LPS injection and blood samples were obtained.

Results: Delivery occurred in preterm (16.2 +/- 0.4 days of gestation) in all LPS-treated mice not administered LF. LF significantly prolonged gestation of LPS-treated mice: LPS + b-LF, 17.8 +/- 0.3 days; LPS + rh-LF, 18.2 +/- 1.3 days (p < 0.05). LF (1 mg/body) significantly suppressed plasma IL-6 in LPS-treated mice: LPS + b-LF, 1060 +/- 154; LPS + rh-LF, 244.2 +/- 59.4; and LPS without LF, 1628 +/- 115 pg/ml (p < 0.05).

Conclusions: rh-LF has an effect of prolongation of gestation in LPS-induced preterm delivery in mice, suppressing LPS-induced plasma IL-6 augmentation.