Nakamura H, Nagase H, Ogino K, Hatta K, Matsuzaki I
Department of Public Health, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa, 920-8640, Japan.
Brain Behav Immun. 2001 Mar;15(1):43-53. doi: 10.1006/brbi.2000.0591.
To clarify whether corticotropin releasing hormone (CRH) and beta-endorphin (betaEP) system mediate maternal immunosuppression in pregnant rats exposed to heat through central or placental pathway, we examined the effects of intravenous (iv) (100 or 500 microg) or intracerebroventricular (icv) (5 microg) administration of CRH receptor antagonist alpha-helical CRH (9-41) on splenic natural killer cell activity (NKCA) as well as betaEP in blood, pituitary lobes, and placenta in pregnant rats at 15 to 16 days gestation. Two-way ANOVA revealed that heat reduced NKCA and elevated blood and pituitary betaEP but did not change placental betaEP. Iv administered 500 microg and icv administered alpha-helical CRH reversed the reduced NKCA and the elevated pituitary betaEP, while iv administration of 100 microg alpha-helical CRH did not. The increased blood betaEP was reversed by iv 100 and 500 microg alpha-helical CRH and icv administration. Both iv and icv administrations reduced placental betaEP independent of heat exposure. Thus, the response of placental betaEP to iv administration of alpha-helical CRH seemed to be stronger than that of pituitary betaEP. These results indicate that alpha-helical CRH which acts on pituitary betaEP antagonizes heat-induced immunosuppression during pregnancy, suggesting that immunosuppression produced by heat stress during pregnancy is mediated by the central CRH system. The placental CRH-betaEP system seems unlikely to be involved in the immunosuppression. Physiologic roles of placental CRH and opioid system should be clarified by future in vitro experiments using placenta specimen including placental immunocyte.
为了阐明促肾上腺皮质激素释放激素（CRH）和β-内啡肽（βEP）系统是否通过中枢或胎盘途径介导热暴露孕鼠的母体免疫抑制，我们检测了静脉注射（iv）（100或500微克）或脑室内（icv）（5微克）给予CRH受体拮抗剂α-螺旋CRH（9-41）对妊娠15至16天的孕鼠脾脏自然杀伤细胞活性（NKCA）以及血液、垂体叶和胎盘中βEP的影响。双向方差分析显示，热降低了NKCA，升高了血液和垂体中的βEP，但未改变胎盘中的βEP。静脉注射500微克和脑室内注射α-螺旋CRH可逆转降低的NKCA和升高的垂体βEP，而静脉注射100微克α-螺旋CRH则不能。静脉注射100和500微克α-螺旋CRH以及脑室内注射可逆转升高的血液βEP。静脉注射和脑室内注射均降低了胎盘中的βEP，且与热暴露无关。因此，胎盘βEP对静脉注射α-螺旋CRH的反应似乎比垂体βEP更强。这些结果表明，作用于垂体βEP的α-螺旋CRH可拮抗孕期热诱导的免疫抑制，提示孕期热应激产生的免疫抑制是由中枢CRH系统介导的。胎盘CRH-βEP系统似乎不太可能参与免疫抑制。胎盘CRH和阿片样物质系统的生理作用应通过未来使用包括胎盘免疫细胞在内的胎盘标本进行的体外实验来阐明。
