抄録
The hypothalamic-pituitary-adrenal (HPA) axis plays a pivotal role in the stress responses. It has been established that certain cytokines, particularly interleukin-1β (IL-1β), can potently stimulate HPA activity. Recent studies have shown that 11,12-EET, a metabolite of cytochrome P-450 (CYP-450) of arachidonic acid cascade, attenuates fever induced by IL-1β in the rat. In this study, we investigated the involvement of CYP-450 metabolite in the plasma ACTH responses to IL-1β administration or immobilization stress. Male Wistar rats were subjected to repeated (daily for 3 days) and single immobilization (2h) or IL-1β administration (5μg/kg, ip). Blood samples were collected immediately after their last immobilization or IL-1β administration. CYP-450 inhibitor, econazole (15 mg/kg ip), or their vehicle was injected 30 min before the stress. Single and repeated immobilization stress or IL-1β administration caused marked increase in the plasma ACTH level. Although econazole has no effect on the IL-1β administration groups, the CYP-450 inhibitor suppressed plasma ACTH elevation in the immobilization stressed groups. These results may indicate that CYP-450 metabolite potentiates HPA axis activity and the involved different mechanisms depend on quality of stressors. [Jpn J Physiol 55 Suppl:S207 (2005)]
