Evidence for an intramedullary prostaglandin-dependent mechanism in the activation of stress-related neuroendocrine circuitry by intravenous interleukin-1.
We have provided evidence that the stimulatory effects of intravenous interleukin-1 (IL-1) on neurosecretory neurons in the paraventricular nucleus (PVH) that express corticotropin-releasing factor (CRF) depend specifically on the integrity of catecholaminergic projections originating in caudal medulla. Here we report on experiments designed to test alternative means by which circulating IL-1 might access medullary aminergic neurons, including mechanisms involving sensory components of the vagus, the area postrema, or perivascular cells bearing IL-1 receptors. Neither abdominal vagotomy nor area postrema lesions reliably altered Fos expression induced in the medulla or PVH in response to a moderately suprathreshold dose of IL-1beta. Cytokine-stimulated increases in CRF mRNA in the PVH were also unaffected by either ablation. By contrast, systemic administration of the cyclooxygenase inhibitor indomethacin resulted in parallel dose-related attenuations of IL-1 effects in hypothalamus and medulla. Microinjections of prostaglandin E2 (PGE2; >/=10 ng) in rostral ventrolateral medulla, the principal seat of IL-1-sensitive neurons that project to the PVH, provoked discrete patterns of cellular activation in hypothalamus and medulla that mimicked those seen in response to intravenous IL-1. We interpret these findings as supporting the hypothesis that paracrine effects of PGE2 released from perivascular cells in the medulla as a consequence of IL-1 stimulation and, acting through prostanoid receptors on or near local aminergic neurons that project to the PVH, contribute to the stimulatory effects of increased circulating IL-1 on neurons constituting the central limb of the hypothalamo-pituitary-adrenal axis.
Ericsson
A
A
Unit of Rheumatology, The Karolinska Hospital, S-171 76 Stockholm, Sweden.
Arias
C
C
Sawchenko
P E
PE
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015167:Vagotomy, Truncal
D007375:Interleukin-1; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; D003346:Corticotropin-Releasing Hormone; D015232:Dinoprostone