Fidel P L, Romero R, Cutright J, Wolf N, Gomez R, Araneda H, Ramirez M, Yoon B H
Department of Obstetrics and Gyncology, Wayne State University School of Medicine, Detroit, Michigan, USA.
J Soc Gynecol Investig. 1997 Jan-Feb;4(1):22-6. doi: 10.1177/107155769700400104.
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.
C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive phosphate-buffered saline (PBS) or lipopolysaccharide (LPS) (50 micrograms/mouse) intraperitoneally (i.p.). Randomly selected PBS- or LPS-treated mice were additionally treated intravenously (i.v.), i.p., or subcutaneously (s.c.) every 3 hours with IL-1ra (1-50 mg) or every 12 hours with sTNFR-Fc (200-400 micrograms) beginning 1 hour before LPS injection. Animals were observed for vaginal bleeding and preterm delivery.
Mice treated i.p. with 50 micrograms 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 i.p. (n = 3) or 200 micrograms sTNFR-Fc every 12 hours i.v. (n = 4) had similar injection-to-delivery intervals as PBS-treated control mice (median 70 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 i.p. 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 i.v. injections of 200 (n = 4) or 400 (n = 9) micrograms 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 i.p. and sTNFR-Fc (200 micrograms) every 12 hours i.v. (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, respectively; P > .05).
The anticytokine agents IL-1ra and sTNFR-Fc did not prevent preterm delivery or prolong pregnancy in endotoxin-induced preterm labor in mice.
确定给予抗细胞因子药物（白细胞介素-1受体拮抗剂（IL-1ra）和可溶性肿瘤坏死因子受体Fc融合蛋白（sTNFR-Fc））是否能预防内毒素诱导的小鼠早产。
将妊娠15天（妊娠70%）的C3H/HeN孕鼠随机分为腹腔注射（i.p.）磷酸盐缓冲盐水（PBS）或脂多糖（LPS）（50微克/只）两组。在LPS注射前1小时开始，随机选择的接受PBS或LPS处理的小鼠每隔3小时静脉注射（i.v.）、腹腔注射或皮下注射（s.c.）IL-1ra（1 - 50毫克），或每隔12小时静脉注射sTNFR-Fc（200 - 400微克）。观察动物是否出现阴道出血和早产情况。
腹腔注射50微克LPS的小鼠（n = 13），其注射至分娩的间隔时间短于腹腔注射PBS的小鼠（n = 19）（中位数分别为13.5小时，范围10 - 105小时与中位数86.8小时，范围53 - 120小时；P < 0.001）。每3小时腹腔注射10毫克IL-1ra的生理盐水处理小鼠（n = 3）或每12小时静脉注射200微克sTNFR-Fc的小鼠（n = 4），其注射至分娩的间隔时间与PBS处理的对照小鼠相似（中位数分别为70小时，范围70 - 76小时与中位数58小时，范围50 - 120小时）。同样，每3小时给予PBS的LPS处理小鼠（n = 20），其注射至分娩的间隔时间与LPS处理小鼠（n = 13）相当（中位数分别为15.5小时，范围9.8 - 92小时与中位数13.5小时，范围10 - 105小时）。每3小时腹腔注射1毫克（n = 4）、10毫克（n = 31）或50毫克（n = 15）IL-1ra的LPS处理小鼠，与LPS处理小鼠（n = 13）相比，其注射至分娩的间隔时间并未延长（中位数分别为11.6、15、14.5和13.5小时；范围分别为10.8 - 12、8 - 95、11 - 92和10 - 105小时）。每12小时静脉注射200微克（n = 4）或400微克（n = 9）sTNFR-Fc的LPS处理小鼠，与LPS处理小鼠（n = 8）相比，其注射至分娩的间隔时间并未延长（中位数分别为23.3、22.5和21.9小时；范围分别为14.8 - 33、15 - 95.5和15.5 - 44小时）。每3小时腹腔注射IL-1ra（10毫克）且每12小时静脉注射sTNFR-Fc（200微克）的LPS处理小鼠（n = 5），其注射至分娩的间隔时间中位数与LPS处理小鼠无差异（中位数分别为26小时，范围24.5 - 72小时与中位数13.5小时，范围10 - 105小时；P > 0.05）。
抗细胞因子药物IL-1ra和sTNFR-Fc不能预防内毒素诱导的小鼠早产或延长孕期。
