Human thioredoxin-1 attenuates the rate of lipopolysaccharide-induced preterm delivery in mice in association with its anti-inflammatory effect.
Maternal intrauterine infection/inflammation represents the major etiology of preterm delivery and the leading cause of neonatal mortality and morbidity. The aim of this study was to investigate the anti-inflammatory properties of thioredoxin-1 in vivo and its potential ability to attenuate the rate of inflammation-induced preterm delivery.



Two intraperitoneal injections of lipopolysaccharide from Escherichia coli were administered in pregnant mice on gestational day 15, with a 3-h interval between the injections. From either 1 h before or 1 h after the first lipopolysaccharide injection, mice received three intravenous injections of either recombinant human thioredoxin-1, ovalbumin, or vehicle, with a 3-h interval between injections.



Intraperitoneal injection of lipopolysaccharide induced a rise of tumor necrosis factor-α, interferon-γ, monocyte chemotactic protein 1, and interleukin-6 in maternal serum levels and provoked preterm delivery. Recombinant human thoredoxin-1 prevented the rise in these proinflammatory cytokine levels. After the inflammatory challenge, placentas exhibited severe maternal vascular dilatation and congestion and a marked decidual neutrophil activation. These placental pathological findings were ameliorated by recombinant human thioredoxin-1, and the rate of inflammation-induced preterm delivery was attenuated.



Thioredoxin-1 may thus represent a novel effective treatment to delay inflammation-induced preterm delivery.
Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Fumihiko
F
Namba
Department of Biological Responses, Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Mikiko
M
Kobayashi-Miura
Department of Surgery, Izumiotsu Municipal Hospital, Osaka, Japan.
Taro
T
Goda
Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Yukiko
Y
Nakura
Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Fumiko
F
Nishiumi
Department of Biological Responses, Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Aoi
A
Son
Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
Akio
A
Kubota
Department of Biological Responses, Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Junji
J
Yodoi
Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Itaru
I
Yanagihara
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000188:drug therapy*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013879:Thioredoxins / Q000494:pharmacology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D013879:Thioredoxins; D007371:Interferon-gamma