Progesterone has been shown to regulate immunity during pregnancy, and progesterone administration may reduce inflammation-induced preterm labor. We sought to determine the maternal brain immune response to LPS-induced inflammation in pregnant and non-pregnant mice and whether additional progesterone supplementation attenuates this response. Pregnant (P: n = 9) and non-pregnant mice (NP: n = 9) were randomized to pretreatment with vaginal progesterone/carrier (Replens), daily from days 13 to 16. On days 15 and 16, LPS/saline was administered by intraperitoneal injection (Replens + saline n = 3; Replens + LPS n = 3; progesterone + LPS n = 3). Mice were sacrificed on day 16 and maternal serum analyzed for IL-6 levels and brains analyzed for nNOS, NF-kB, IL-6 protein levels and for immature myeloid cells (IMCs) and microglial activity. LPS significantly increased brain nNOS, NF-kB, and IL-6 in both NP and P mice, with significantly greater responses in P mice. In both NP and P groups, progesterone significantly attenuated LPS-induced increase of nNOS and NF-kB, however with no effect on serum IL-6. In the NP brains, LPS significantly increased IMC population and progesterone reduced the IMC phenotype to levels similar to controls. In P mice, neither LPS nor LPS + progesterone altered the brain IMC population. LPS significantly increased the microglial activity in both NP and P groups, which was attenuated by progesterone. Progesterone attenuates brain inflammatory response to LPS in both NP and P mice although it has no effect on systemic inflammation. In NP mice, progesterone attenuated the increase in brain IMC following LPS administration. Our results suggest that endogenous progesterone during pregnancy may protect the brain from LPS-induced inflammation.

黄体酮已被证明可以调节怀孕期间的免疫力，并且黄体酮的施用可以减少炎症引起的早产。我们试图确定怀孕和非怀孕小鼠的母体大脑对脂多糖诱导的炎症的免疫反应，以及额外补充黄体酮是否会减弱这种反应。怀孕 (P: n = 9) 和非怀孕小鼠 (NP: n = 9) 被随机分配接受阴道孕酮/载体 (Replens) 预处理，从第 13 天到第 16 天每天一次。在第 15 天和第 16 天，LPS/盐水通过腹腔注射给药（Replens + 生理盐水n = 3；Replens + LPS n = 3；黄体酮 + LPS n = 3）。第 16 天处死小鼠，分析母体血清的 IL-6 水平，分析大脑的 nNOS、NF-kB、IL-6 蛋白水平以及未成熟骨髓细胞 (IMC) 和小胶质细胞活性。 LPS 显着增加 NP 和 P 小鼠大脑中的 nNOS、NF-kB 和 IL-6，其中 P 小鼠的反应显着更大。在 NP 组和 P 组中，孕酮均显着减弱 LPS 诱导的 nNOS 和 NF-kB 增加，但对血清 IL-6 没有影响。在 NP 大脑中，LPS 显着增加了 IMC 数量，而黄体酮则将 IMC 表型降低至与对照组相似的水平。在 P 小鼠中，LPS 和 LPS + 黄体酮均不会改变大脑 IMC 数量。 LPS 显着增加了 NP 组和 P 组的小胶质细胞活性，而黄体酮则减弱了这种活性。黄体酮可减弱 NP 和 P 小鼠脑部对 LPS 的炎症反应，但对全身炎症没有影响。在 NP 小鼠中，黄体酮减弱了 LPS 给药后大脑 IMC 的增加。 我们的结果表明，怀孕期间的内源性黄体酮可能会保护大脑免受脂多糖诱导的炎症的影响。