Recombinant human lactoferrin has preventive effects on lipopolysaccharide-induced preterm delivery and production of inflammatory cytokines in mice

Objective: The following animal studies have been conducted to investigate whether recombinant human lactoferrin (rh-LF) has the same effect as bovine lactoferrin (b-LF) in the prevention of preterm delivery. Study Design: Female C3H/HeNCrj mice were pair-mated with male Crj:B6D2F1 mice. On day 15 of gestation, as a model of preterm delivery, a 50 mu g/kg intraperitoneal injection of lipopolysaccharide, (LPS) was administered twice with a 3-h interval between injections (2:00 and 5:00 PM). One hour prior to each LPS injection (1:00 and 4:00 PM), 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 4 times (1:00, 2:00, 4:00 and 5:00 PM). Body weights and delivery times were recorded. To compare plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) between experimental and other pregnant mice, prepared as above, were sacrificed 6 h after the second LIPS injection, and then blood samples were obtained and analyzed. Results: Preterm delivery occurred (16.2 +/- 0.4 days of gestation) in all LPS-treated mice that were not administered LF LF significantly prolonged gestation of LPS-treated mice: b-LF+LPS, 17.8 +/- 0.3 days; rh-LF+LPS, 18.0 +/- 0.8 days (P<0.05). LF (1 mg/body) significantly suppressed plasma IL-6 in LPS-treated mice: b-LF+LPS, 1060 +/- 154; rh-LF+ LPSF, 244 +/- 59; LPS without LF, 1628 +/- 115 pg/mL (P<0.05). As well, LF (1 mg/body) significantly suppressed plasma TNF-alpha in LPS-treated mice: b-LF+LPS, 88 +/- 36; rh-LF+LPS, 37 +/- 30; LPS without LF, 114 +/- 49 pg/mL (P<0.05). Conclusions: Rh-LF may prolong gestation in LPS-induced preterm delivery in mice, by suppressing LPS-induced plasma IL-6 and TNF-alpha augmentation.