Indomethacin attenuates oxytocin and hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1 beta.
Systemic administration of the cytokine IL-1 beta produces a significant release of ACTH into the plasma and activation of hypothalamic oxytocin (OT) and corticotropin releasing factor (CRF) cells. However, the mechanism(s) by which systemic IL-1 beta induces these responses is not clear. In the present study, we have investigated the proposal that catecholamine cells of the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS) can relay circulating IL-1 signals via a prostaglandin-dependent mechanism to effect the HPA axis responses in the rat. Intra-arterial administration of IL-1 beta (1 pg/kg) to otherwise untreated animals produced a prominent release of ACTH into the plasma, substantial c-fos expression in paraventricular medial parvocellular (mPVN) corticotropin releasing factor (CRF) cells, supraoptic (SON) and paraventricular nucleus (PVN) OT cells, area postrema cells, NTS and VLM catecholamine cells and cells of the central amygdala. Pretreatment with the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg body weight ia) 15 min before IL-1 beta administration (1 pg/kg ia) significantly reduced plasma ACTH release and c-fos expression in PVN and SON OT cells and MPVN CRF cells, in addition, the area postrema, A1 and C1 catecholamine cell groups of the VLM and A2 and C2 catecholamine cell groups of the NTS, all exhibited concomitant reductions in c-fos expression. Conversely indomethacin administration did not alter the IL1 beta-induced expression of c-fos in the central amygdala. These data suggest that central pathways involved in the IL-1 beta-induced activation of the HPA axis and OT cells are, at least in part, dependent upon prostaglandin synthesis. It is proposed that neurons in the area postrema, NTS and VLM might mediate this IL-1 beta-induced activation of hypothalamic CRF and OT cells and release of ACTH into the plasma.
Department of Physiology and Pharmacology, University of Queensland, Australia.
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D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D007031:Hypothalamus / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000378:metabolism
D002395:Catecholamines; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D007213:Indomethacin