Prevention of human recombinant interleukin-1 beta (rhIL-1 beta) embryolethality with progesterone or indomethacin.
Prevention of human recombinant interleukin-1 beta (rhIL-1 beta) embryolethality with progesterone or indomethacin.
复制标题
用黄体酮或吲哚美辛预防人重组白细胞介素 1 β (rhIL-1 β) 胚胎致死率。
DOI：
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发表时间：
1995
影响因子：
3.6
通讯作者：
D. Tracy
中科院分区：
文献类型：
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作者：
T. Marks;D. Tracy
问题
在早期研究中发现，当在妊娠第10天对Crl：TUC（SD）spf（TUC）大鼠给药时，溴匹立明和替洛龙具有胚胎致死性。孕酮或吲哚美辛可以，至少部分地，防止这种影响。免疫调节剂似乎模拟了PGF 2 α的黄体溶解作用，导致黄体孕酮释放停止，随后母体对妊娠子宫的支持中断，胚胎死亡。由于溴匹立明已被证明可诱导白细胞介素-1，并且已发现该细胞因子可增加人蜕膜细胞中的PGF 2 α水平，因此决定研究人白细胞介素-1 β是否可能以类似于溴匹立明和替洛龙的方式起作用。
方法
将溴匹立明（400 mg/kg，p.o.）或rhIL-1 β（20、30或40微克/kg，s.c.）Crl：CD[BR]（CD）或TUC大鼠在妊娠第10天单独和与孕酮（2 mg/kg/天，s.c.）或吲哚美辛（0.6mg/天，s.c.，第9-11天）。在妊娠第14天处死母鼠，检查其子宫内容物。
结果
当在妊娠第10天给予CD或TUC大鼠时，rhIL-1 β（30-40 μ g/kg）具有胚胎致死性。孕激素或吲哚美辛联合给药至少部分预防了TUC大鼠给予rhIL-1 β（30 μ g/kg）时观察到的胚胎死亡。
结论
获得的证据支持的假设，白细胞介素-1参与胚胎致死的行动的免疫调节剂溴匹立明和替洛龙。
PROBLEM
Bropirimine and tilorone were found in earlier studies to be embryolethal when administered to Crl:TUC(SD)spf (TUC) rats on gestation day 10. Progesterone or indomethacin could, at least partially, prevent this effect. The immunomodulators appeared to mimic the luteolytic effects of PGF2 alpha, resulting in a shutdown in progesterone release by the corpora lutea, followed by a disruption in maternal support to the pregnant uterus and embryolethality. Since bropirimine has been shown to induce interleukin-1, and since this cytokine has been found to increase PGF2 alpha levels in human decidual cells, the decision was made to investigate whether human interleukin-1 beta might act in an analogous manner to bropirimine and tilorone.
METHOD
Bropirimine (400 mg/kg, p.o.) or rhIL-1 beta (20, 30, or 40 micrograms/kg, s.c.) was administered on gestation day 10 to Crl:CD[BR] (CD) or TUC rats, alone and in combination with progesterone (2 mg/kg/day, s.c.) or indomethacin (0.6 mg/day, s.c., days 9-11). On gestation day 14 the dams were killed and their uterine contents examined.
RESULTS
rhIL-1 beta (30-40 micrograms/kg) was embryolethal when administered to CD or TUC rats on gestation day 10. Progesterone or indomethacin coadministration prevented, at least partially, the embryolethality seen when rhIL-1 beta was administered (30 micrograms/kg) to TUC rats.
CONCLUSION
Evidence was obtained in support of the hypothesis that interleukin-1 is involved in the embryolethal actions of the immunomodulators bropirimine and tilorone.