Selgas L, Pazo D, Arce A, Esquifino AI, Cardinali DP
Departamento de Bioquimica y Biologia Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Biol Signals. 1998 Jan;7(1):15-24.
The effect of Freund's adjuvant injection on 24-hour variation in circulating ACTH, prolactin, growth hormone (GH) and thyroid-stimulating hormone (TSH) levels, and of hypothalamic norepinephrine (NE) content and dopamine (DA) and serotonin (5HT) turnover was examined in adult rats. In control rats, serum ACTH and prolactin exhibited peak values at the light-dark transition while the maximum in TSH was found in the late afternoon. GH levels did not vary on a 24-hour basis. In Freund's-adjuvant-injected rats, 24-hour variations in TSH levels became blunted while 24-hour variations in prolactin and ACTH persisted. Freund's adjuvant treatment augmented serum ACTH and prolactin levels, and decreased GH and TSH levels. Hypothalamic NE content, and turnover of DA and 5HT varied on a 24-hour basis in rats receiving adjuvant's vehicle. The NE content of the anterior, medial and posterior hypothalamus peaked at 04.00 h, while that of the median eminence attained its maximum at 16.00-20.00 h. Maxima in hypothalamic DA and 5HT turnover ocurred at 04.00 h regardless of the region examined. In Freund's-adjuvant-injected rats, reduced amplitude of daily variations of NE content in the median eminence and anterior and medial hypothalamus, as well as a phase advance in the 24-hour rhythm of the posterior hypothalamic NE content were seen. Mycobacterial adjuvant injection also reduced the amplitude of circadian rhythm in hypothalamic 5HT turnover, shifted the maximum in median eminence DA turnover towards light-dark transition, and decreased the amplitude of DA turnover rhythm in the anterior, medial and posterior hypothalamus. Administration of the immunosuppressant drug cyclosporine restored the augmented ACTH and prolactin levels and the depressed GH and TSH levels found in Freund's-adjuvant-injected rats. Cyclosporine was also effective to restore 24-hour rhythmicity of serum ACTH and TSH, but not of prolactin levels. Immunosuppression restored rhythmicity of NE content and of DA and 5HT turnover in anterior, medial and posterior hypothalamic regions. Cyclosporine did not modify the effect of Freund's adjuvant on median eminence but in was able to counteract the changes in the DA and 5HT turnover in the median eminence found after immunization. The results are in accord with a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on ACTH, GH, prolactin and TSH release mechanisms, which was partially sensitive to immunosuppression induced by cyclosporine.
研究了弗氏佐剂注射对成年大鼠循环促肾上腺皮质激素（ACTH）、催乳素、生长激素（GH）和促甲状腺激素（TSH）水平24小时变化的影响，以及对下丘脑去甲肾上腺素（NE）含量、多巴胺（DA）和5-羟色胺（5HT）周转的影响。在对照大鼠中，血清ACTH和催乳素在明暗交替时呈现峰值，而TSH的最大值出现在下午晚些时候。GH水平在24小时内无变化。在注射弗氏佐剂的大鼠中，TSH水平的24小时变化变得平缓，而催乳素和ACTH的24小时变化持续存在。弗氏佐剂治疗使血清ACTH和催乳素水平升高，使GH和TSH水平降低。在接受佐剂载体的大鼠中，下丘脑NE含量以及DA和5HT的周转在24小时内变化。下丘脑前部、中部和后部的NE含量在04:00时达到峰值，而正中隆起的NE含量在16:00 - 20:00时达到最大值。无论检查哪个区域，下丘脑DA和5HT周转的最大值均出现在04:00时。在注射弗氏佐剂的大鼠中，观察到正中隆起以及下丘脑前部和中部的NE含量每日变化幅度减小，以及下丘脑后部NE含量的24小时节律出现相位提前。注射分枝杆菌佐剂还降低了下丘脑5HT周转的昼夜节律幅度，使正中隆起DA周转的最大值向明暗交替方向移动，并降低了下丘脑前部、中部和后部DA周转节律的幅度。给予免疫抑制剂环孢素可恢复注射弗氏佐剂大鼠中升高的ACTH和催乳素水平以及降低的GH和TSH水平。环孢素也有效地恢复了血清ACTH和TSH的24小时节律性，但对催乳素水平无效。免疫抑制恢复了下丘脑前部、中部和后部区域NE含量以及DA和5HT周转的节律性。环孢素未改变弗氏佐剂对正中隆起的作用，但能够抵消免疫后在正中隆起发现的DA和5HT周转的变化。结果表明，弗氏佐剂注射后早期免疫介导的炎症反应对ACTH、GH、催乳素和TSH释放机制有显著影响，这种影响对环孢素诱导的免疫抑制部分敏感。
