Treatment with the interleukin-I receptor antagonist and soluble tumor necrosis factor receptor Fc fusion protein does not prevent endotoxin-induced preterm …
The Journal of the Society for Gynecologic Investigation: JSGI, 1997•Springer
Objective To determine whether the administration of anticytokine agents, the interleukin-1
receptor antagonist (IL-1ra) and a soluble tumor necrosis factor receptor Fc fusion protein
(sTNFR-Fc), prevents endotoxin-induced preterm delivery in mice. Methods C3H/HeN
pregnant mice at 15 days of gestation (70% gestation) were randomized to receive
phosphate-buffered saline (PBS) or lipopolysaccharide (LPS)(50 μg/mouse)
intraperitoneally (ip). Randomly selected PBS-or LPS-treated mice were additionally treated …
receptor antagonist (IL-1ra) and a soluble tumor necrosis factor receptor Fc fusion protein
(sTNFR-Fc), prevents endotoxin-induced preterm delivery in mice. Methods C3H/HeN
pregnant mice at 15 days of gestation (70% gestation) were randomized to receive
phosphate-buffered saline (PBS) or lipopolysaccharide (LPS)(50 μg/mouse)
intraperitoneally (ip). Randomly selected PBS-or LPS-treated mice were additionally treated …
Abstract
Objective
To determine whether the administration of anticytokine agents, the interleukin-1 receptor antagonist (IL-1ra) and a soluble tumor necrosis factor receptor Fc fusion protein (sTNFR-Fc), prevents endotoxin-induced preterm delivery in mice.
Methods
C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive phosphate-buffered saline (PBS) or lipopolysaccharide (LPS)(50 μg/mouse) intraperitoneally (ip). Randomly selected PBS-or LPS-treated mice were additionally treated intravenously (iv), ip, or subcutaneously (sc) every 3 hours with IL-1ra (1–50 mg) or every 12 hours with sTNFR-Fc (200–400 μg) beginning 1 hour before LPS injection. Animals were observed for vaginal bleeding and preterm delivery.
Results
Mice treated ip with 50 μg LPS (n= 13) had a shorter injection-to-delivery interval than mice treated similarly with PBS (n= 19)(median 13.5 hours, range 10–105 versus median 86.8 hours, range 53–120, respectively; P<. 001). Saline-treated mice given 10 mg IL-1ra every 3 hours ip (n= 3) or 200 μg sTNFR-Fc every 12 hours iv (n= 4) had similar injection-to-delivery intervals as PBS-treated control mice (median 10 hours, range 70–76 versus median 58 hours, range 50–120, respectively). Similarly, LPS-treated mice given PBS every 3 hours (n= 20) had injection-to-delivery intervals comparable to LPS-treated mice (n= 13)(median 15.5 hours, range 9.8–92 versus median 13.5 hours, range 10–105, respectively). Lipopolysaccharide-treated mice given ip injections of 1 (n= 4), 10 (n= 31), or 50 (n= 15) mg of IL-1ra every 3 hours did not have longer injection-to-delivery intervals compared with LPS-treated mice (n= 13)(medians 11.6, 15, 14.5, and 13.5 hours; ranges 10.8–12, 8–95, 11–92, and 10–105, respectively). Lipopolysaccharide-treated mice given iv injections of 200 (n= 4) or 400 (n= 9) μg sTNFR-Fc every 12 hours did not have longer injection-to-delivery intervals compared with LPS-treated mice (n= 8)(medians 23.3, 22.5, and 21.9 hours; ranges 14.8–33, 15–95.5, and 15.5–44, respectively). The median injection-to-delivery interval of LPS-treated mice given both IL-1ra (10 mg) every 3 hours ip and sTNFR-Fc (200 μg) every 12 hours iv (n= 5) was not different from that of LPS-treated mice (median 26 hours, range 24.5–72 versus median 13.5 hours, range 10–105, respectwely; P>. 05).
Conclusion
The anticytokine agents IL-1ra and sTNFR-Fc did not prevent preterm delivery or prolong pregnancy in endotoxin-induced preterm labor in mice.
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