title: Recombinant human lactoferrin has preventive effects on lipopolysaccharide-induced preterm delivery and production of inflammatory cytokines in mice.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8, Hatanodai, Tokyo, 142-8666, Japan. otsuki@med.showa-u.ac.jp
authors.forename: Katsufumi
authors.initials: K
authors.lastname: Otsuki
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yakuwa
authors.forename: Maki
authors.initials: M
authors.lastname: Sawada
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Kaori
authors.initials: K
authors.lastname: Mitsukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Chiba
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nagatsuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Okai
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007781:Lactoferrin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin