Role of urinary trypsin inhibitor in the maintenance of pregnancy in mice.
OBJECTIVE
To investigate the mechanisms whereby urinary trypsin inhibitor prevents lipopolysaccharide-induced preterm delivery in mice.


METHODS
On day 15 of pregnancy, C3H/HeNCrg female mice impregnated by Crg:B6D2F1 male mice were treated intraperitoneally with lipopolysaccharide (50 micrograms/kg, twice at a 3-hour interval) to induce preterm delivery. Urinary trypsin inhibitor (2.5 x 10(4), 7.5 x 10(4), or 25 x 10(4) units/kg, ten times at 1-hour intervals) or saline solution was administered intraperitoneally to the animals.


RESULTS
The incidence of preterm delivery was significantly decreased on a dose-related basis by urinary trypsin inhibitor treatment. Urinary trypsin inhibitor prevented the morphologic and functional changes in fetal membranes and cervical ripening preceding the onset of preterm delivery. Urinary trypsin inhibitor also suppressed the increase in plasma and amniotic fluid concentrations of interleukin-1 alpha, interleukin-6, and tumor necrosis factor-alpha after the lipopolysaccharide dosing in this animal model for preterm delivery.


CONCLUSIONS
Urinary trypsin inhibitor prevents the pathogenicity of preterm delivery through the suppression of cytokine production.
Kaga
N
N
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Katsuki
Y
Y
Futamura
Y
Y
Obata
M
M
Shibutani
Y
Y
D000818:Animals; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D007378:Interleukins / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D007752:Obstetric Labor, Premature / Q000503:physiopathology; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000187:drug effects / Q000502:physiology*; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D014361:Trypsin Inhibitors / Q000494:pharmacology / Q000502:physiology*
D006023:Glycoproteins; D007378:Interleukins; D014361:Trypsin Inhibitors; C028665:urinastatin