Interleukin-1ß (IL-1ß) level is modulated during multiple stress reactions in both brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis regulation and peripheral systems. Multiple distinct stressors induce different IL-1ß and HPA axis responses. The purpose of the present study was to determine if the effect of prior repeated restraint stress on IL-1ß levels in prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on alterations induced in HPA-axis responses. Experiments were performed on male Wistar rats which were exposed to 10 min restraint stress twice a day for 3 days. Twentyfour hour after the last stress period rats were injected i.p. with a single dose of IL-1ß, IL-1ß receptor antagonist or saline. After rapid decapitation, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen at -70°C. Total IL-1ß, ACTH and corticosterone (CORT) levels were determined in plasma using commercially available kits. Western blot analyses were performed on brain structures samples. Repeated restraint for 3 days alone substantially augmented the resting plasma levels of both IL-1ß, ACTH and CORT 24 h after the last restraint. Pretreatment with IL-1ß antagonist abolished the increase in ACTH and CORT responses to repeated stress. IL-1ß receptor antagonist also reduced the enhancement of plasma CORT level induced by 10 min stress. This suggests the selectivity of IL-1ß receptors in central and peripheral mechanisms modulating the stress-induced HPA axis responses. These results suggest that repeated stress increases IL-1ß production which activates ACTH and CORT secretion. Repeated stress also markedly enhanced IL-1ß level in brain structures involved in HPA axis regulation. The present results support the role of brain and peripheral IL-1ß in adaptation of HPA response during prolonged stress. Grant: POIG 01.01.02-12-004/09-00 financed by European Regional Development Fund.
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