McClure L, O'Connor A E, Hayward S, Jenkin G, Walker D W, Phillips D J
Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.
J Endocrinol. 2005 Apr;185(1):139-49. doi: 10.1677/joe.1.06051.
The release of activin A in response to intravenous injection of the bacterial cell-wall component lipopolysaccharide (LPS) was investigated in an ovine model of acute inflammatory challenge in newborn and adult sheep, and in non-pregnant and pregnant ewes. Neonatal lambs (<20 days of age) showed a quantitatively similar response in terms of circulating concentrations of activin A, its binding protein follistatin and the cytokine interleukin-6 compared with adult ewes challenged with an equivalent dose (300 ng/kg bodyweight) of LPS. The fever response and plasma tumour necrosis factor-alpha release in response to LPS, however, were significantly (P < 0.01) less in lambs than in the adult group. Pregnant ewes in the last trimester of gestation had similar responses to LPS, in all aspects measured, compared with their non-pregnant counterparts, apart from an ablated fever response. Although the adult and neonatal sheep responded to LPS, a similar response was not apparent in the fetal circulation, possibly due to a protective effect of the placenta. A 10-fold increase in the dose of LPS (from 300 ng to 3 microg/kg bodyweight) given to neonatal lambs elicited an increase in several cytokine responses measured, with a significant (P< 0.05) increase in follistatin release. In contrast, the amount of activin released by the increased dose of LPS was similar to that invoked by the lower dose. The effect of tolerance to LPS was investigated by giving a second challenge of LPS 5 days after the initial injection. In all animals studied, there was an ablated (P < 0.05) response to the subsequent LPS injection, apart from a similar temperature-response profile. These data provide further evidence that activin A concentrations in the bloodstream are acutely responsive to inflammatory challenge in post-natal life and suggest that the response forms a significant component of the innate immune system.
在新生羊和成年羊、未孕母羊和孕羊的急性炎症激发绵羊模型中，研究了静脉注射细菌细胞壁成分脂多糖（LPS）后激活素A的释放情况。与接受同等剂量（300 ng/kg体重）LPS激发的成年母羊相比，新生羔羊（<20日龄）在激活素A的循环浓度、其结合蛋白卵泡抑素和细胞因子白细胞介素-6方面表现出数量上相似的反应。然而，羔羊对LPS的发热反应和血浆肿瘤坏死因子-α释放明显（P<0.01）低于成年组。妊娠晚期的孕羊在所有测量方面对LPS的反应与未孕母羊相似，但发热反应消失。尽管成年羊和新生羊对LPS有反应，但在胎儿循环中未观察到类似反应，这可能是由于胎盘的保护作用。给新生羔羊注射的LPS剂量增加10倍（从300 ng增加到3 μg/kg体重）会引起所测几种细胞因子反应增加，卵泡抑素释放显著（P<0.05）增加。相比之下，高剂量LPS释放的激活素量与低剂量引起的相似。通过在首次注射LPS 5天后再次注射LPS来研究对LPS的耐受作用。在所有研究的动物中，除了类似的温度反应曲线外，对随后的LPS注射反应均消失（P<0.05）。这些数据进一步证明，出生后血液中激活素A浓度对炎症激发有急性反应，并表明该反应是先天免疫系统的重要组成部分。
