Katsufumi Otsuki, Kyoko Yakuwa, Maki Sawada, Akitoshi Hasegawa, Yasushi Sasaki, Kaori Mitsukawa, Hiroshi Chiba, Masaaki Nagatsuka, Hiroshi Saito, Takashi Okai
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 ?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-? (TNF-?) 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-? 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-? augmentation.
Journal of Perinatal Medicine, Walter de Gruyter
Print ISSN: 1619-3997
Volume: 33, 07/2005
Pages: 320 - 323
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