Recombinant human lactoferrin inhibits matrix metalloproteinase (MMP-2, MMP-3, and MMP-9) activity in a rabbit preterm delivery model.

AIM: To investigate the effect of recombinant human lactoferrin (rh-LF) on the expression of matrix metalloproteinase as a marker of cervical maturation, using a rabbit preterm delivery model in which preterm labor was induced by bacteria. METHODS: We used cervical tissues that had been excised in a previous study in which rabbits were randomly assigned to receive either inoculation with Escherichia coli (E. coli) or saline solution and to receive pretreatment with or without rh-LF inserted into the cervix two hours before bacterial inoculation (Condition A: saline + saline; Condition B: rh-LF + E. coli; Condition C: saline +E. coli). E. coli, saline solution, and rh-LF were inserted into the cervix using a hysteroscope and a sterile polyethylene cannula. Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out and preserved, and expression of matrix metalloproteinases MMP-2,-3, and -9 in the cervix was evaluated using Western blot. RESULTS: MMP-2,-3, and -9 levels in the cervix under Conditions A and B were significantly lower than that under Condition C. CONCLUSIONS: These results suggest that the prevention of preterm delivery by rh-LF in a rabbit model has been achieved through inhibition of cervical maturation promoted by matrix metalloproteinase activity.

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 microg/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 LPS 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.