TREATMENT WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST AND SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR FC FUSION PROTEIN DOES NOT PREVENT ENDOTOXIN-INDUCED PRETERM PARTURITION IN MICE

OBJECTIVE: To determine whether the administration of anticytokine age nts, the interleukin-1 receptor antagonist (IL-1ra) and a soluble tumo r necrosis factor receptor Fc fusion protein (sTNFR-Fc), prevents endo toxin-induced preterm delivery in mice. METHODS: C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive ph osphate-buffered saline (PBS) or lipopolysaccharide (LPS) (50 mu g/mou se) intraperitoneally (i.p.). Randomly selected PBS- or LPS-treated mi ce were additionally treated intravenously (i.v.), i.p., or subcutaneo usly (s.c.) every 3 hours with IL-1ra (1-50 mg) or every 12 hours with sTNFR-Fc (200-400 mu g) beginning 1 hour before LPS injection. Animal s were observed for vaginal bleeding and preterm delivery. RESULTS: Mi ce treated i.p. with 50 mu g LPS (n = 13) had a shorter injection-to-d elivery interval than mice treated similarly with PBS (n = 19) (median 13.5 hours, range 10-105 versus median 86.8 hours, range 53-120, resp ectively, P <.001). Saline-treated mice given 10 mg IL-1ra every 3 hou rs i.p. (n = 3) or 200 mu g sTNFR-Fc every 12 hours i.v. (n = 4) had s imilar injection-to-delivery intervals as PBS-treated control mice (me dian 70 hours, range 70-76 versus median 58 hours, range 50-120, respe ctively). 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, rang e 10-105, respectively). Lipopolysaccharide-treated mice given i.p. in jections 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 w ith 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). Lipopolysacch aride-treated mice given i.v. injections of 200 (n = 4) or 400 (n = 9) mu g sTNFR-Fc every 12 hours did not have longer injection-to-deliver y 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 b oth IL-1ra (10 mg) every 3 hours i.p. and sTNFR-Fc (200 mu g) every 12 hours i.v. (n = 5) was riot different from that of LPS-treated mice ( median 26 hours, range 24.5-72 versus median 13.5 hours, range 10-105, respectively; P>.05). CONCLUSION: The anticytokine agents IL-1ra and sTNFR-Fc did not prevent preterm delivery or prolong pregnancy in endo toxin-induced preterm labor in mice. Copyright (C) 1997 by the Society for Gynecologic Investigation.