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.
Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, Japan. ysasaki-md@med.showa-u.ac.jp
Yasushi
Y
Sasaki
Katsufumi
K
Otsuki
Akitoshi
A
Hasegawa
Maki
M
Sawada
Hiroshi
H
Chiba
Momoko
M
Negishi
Masaaki
M
Nagatsuka
Takashi
T
Okai
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D051379:Mice; D008809:Mice, Inbred C3H; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007781:Lactoferrin