Esquifino A I, Selgas L, Vara E, Arce A, Cardinali D P
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, España.
Biol Signals Recept. 1999 May-Jun;8(3):178-90. doi: 10.1159/000014588.
The effect of Freund's adjuvant injection on 24-hour variation of hypothalamic corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), GH-releasing hormone (GRH) and somatostatin levels was examined in adult rats kept under light between 0800 and 2000 h daily. Groups of rats receiving Freund's complete adjuvant or its vehicle 3 days before sacrifice were killed at six different time intervals throughout a 24-hour cycle. In the median eminence, adjuvant vehicle-injected rats exhibited significant 24-hour variations for the four hormones examined, with maxima at noon. These 24-hour rhythms were inhibited or suppressed by Freund's adjuvant injection. In the anterior hypothalamus of adjuvant vehicle-treated rats, CRH content peaked at 1600 h, while two peaks were found for TRH and GRH levels, i.e., at 2400-0400 h and 1600 h. Freund's adjuvant injection suppressed 24-hour rhythm of anterior hypothalamic CRH, TRH and GRH content and uncovered a peak in anterior hypothalamic somatostatin levels at 0400 h. In the medial hypothalamus of adjuvant vehicle-treated rats, significant 24-hour variations were detectable for TRH (peaks at 1600 and 2400 h) and somatostatin (peak at 2400 h) which disappeared after Freund's adjuvant injection. In the posterior hypothalamus of adjuvant vehicle-treated rats, two peaks were apparent for CRH, TRH and somatostatin levels, i.e. at 1600 h and 2400-0400 h, this hormonal profile remaining unmodified after Freund's adjuvant administration. The administration of the immunosuppressant drug cyclosporine (5 mg/kg, 5 days) impaired the depressing effect of Freund's adjuvant injection on CRH, TRH and somatostatin content in median eminence, but not that on GRH. In the anterior hypothalamus, cyclosporine generally prevented the effect of immunization on hormone levels an revealed a second maximum in TRH at 0400 h. Cyclosporine also restored 24-hour variations in TRH and somatostatin levels of medial hypothalamus of Freund's adjuvant-injected rats but was unable to modify them in the posterior hypothalamus. The results further support the existence of a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on hypothalamic levels which was partially sensitive to immunosuppression by cyclosporine.
在每天08:00至20:00处于光照条件下的成年大鼠中，研究了弗氏佐剂注射对下丘脑促肾上腺皮质激素释放激素（CRH）、促甲状腺激素释放激素（TRH）、生长激素释放激素（GRH）和生长抑素水平24小时变化的影响。在处死前3天接受弗氏完全佐剂或其赋形剂的大鼠组，在24小时周期内的六个不同时间间隔处死。在正中隆起，注射佐剂赋形剂的大鼠所检测的四种激素呈现显著的24小时变化，中午达到最大值。这些24小时节律被弗氏佐剂注射抑制或压制。在接受佐剂赋形剂处理的大鼠下丘脑前部，CRH含量在16:00达到峰值，而TRH和GRH水平出现两个峰值，即0:00 - 4:00和16:00。弗氏佐剂注射抑制了下丘脑前部CRH、TRH和GRH含量的24小时节律，并在4:00发现下丘脑前部生长抑素水平出现一个峰值。在接受佐剂赋形剂处理的大鼠下丘脑中部，TRH（峰值在16:00和24:00）和生长抑素（峰值在24:00）呈现显著的24小时变化，在弗氏佐剂注射后消失。在接受佐剂赋形剂处理的大鼠下丘脑后部，CRH、TRH和生长抑素水平出现两个峰值，即16:00和0:00 - 4:00，在给予弗氏佐剂后这种激素谱未改变。给予免疫抑制药物环孢素（5mg/kg，5天）削弱了弗氏佐剂注射对正中隆起CRH、TRH和生长抑素含量的抑制作用，但对GRH没有影响。在下丘脑前部，环孢素总体上阻止了免疫对激素水平的影响，并在4:00发现TRH的第二个最大值。环孢素还恢复了弗氏佐剂注射大鼠下丘脑中部TRH和生长抑素水平的24小时变化，但在下丘脑后部无法改变它们。结果进一步支持了弗氏佐剂注射后早期免疫介导的炎症反应对下丘脑水平有显著影响，且这种影响对环孢素免疫抑制部分敏感。
