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After intracerebroventricular administration, both interleukin-1 alpha and corticotropin-releasing hormone increase nociceptive thresholds evaluated by the hot-plate test in the rat. Pretreatment with 6-hydroxydopamine or prazosin fully prevents the action of both substances. Moreover, the effect of interleukin-1 alpha is completely blocked by the intracerebroventricular administration of the corticotropin-releasing hormone antagonist alpha-helical CRH 9-41. Our results suggest an involvement of CRH and the noradrenergic system in the antinociceptive effect of central interleukin-1 alpha.

In order to evaluate the effects in adults of different doses of ACTH 1-17 on the cortisol and aldosterone secretion, 200 micrograms of ACTH 1-17 were injected i.m. at 07(00) in two groups of 6 patients each of both sexes. Sampling was done before and after ACTH 1-17 administration at 4-h intervals from 08(00) to 04(00) in order to define the circadian profiles of both cortisol and aldosterone. At the time of study all subjects were kept under the same routine conditions. The i.m. injection of 100 micrograms of ACTH 1-17 was followed by a maximum response of cortisol which coincided with the physiological circadian peak of the hormone (511.7 +/- 122.7 vs 195.5 +/- 92.9 ng/ml; mean +/- 1 SD; p less than 0.001). With this treatment no variations in the normal circadian rhythm were observed. After the injection of 200 micrograms ACTH 1-17, a marked variation in the circadian rhythm of cortisol (peak at 16(00): 390.0 +/- 49.8 ng/ml; mean +/- 1 SD) was observed. Significant variations in the circadian rhythm of aldosterone with respect to the normal profile were observed only after the injection of 200 micrograms ACTH 1-17 (peak at 16(00): 137.5 +/- 50.5 vs 50.8 +/- 36.1 ng/ml; mean +/- 1 SD; p less than 0.01). The hormone increase observed after the injection of 100 micrograms (peak at 08(00): 111.7 +/- 87.5 vs 61.3 +/- 16.5 ng/ml; mean +/- 1 SD) was not statistically significant. Our results indicate that the clinical use of ACTH 1-17 i.m. is not recommended at doses greater than 100 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)