Endotoxin-stimulated production of rat hypothalamic interleukin-1 beta in vivo and in vitro, measured by specific immunoradiometric assay.
Regulation of a number of aspects of the acute-phase response, including induction of fever and activation of the hypothalamo-pituitary-adrenal axis, occurs within the hypothalamus. The acute-phase response appears to be co-ordinated by the inflammatory cytokine interleukin-1 (IL-1). A number of studies using hybridization techniques to measure IL-1 gene expression and immunocytochemistry to localize immunoactive IL-1 have established the concept that the central nervous system, and in particular the hypothalamus, is a site of IL-1 production, and that levels increase in response to inflammatory stimuli. In this report we present data on the levels of IL-1 beta produced in the rat hypothalamus using quantitative immunoassay techniques. Bacterial endotoxin, administered to rats in vivo, evoked increases in hypothalamic IL-1 beta levels which were significant within 1 h, and reached maximum levels at 5-10 h. The response to endotoxin was dose-related, and levels reached in hypothalamic extracts corresponded to intrahypothalamic levels of the order of 20 ng/ml. During short-term in-vitro culture of rat hypothalami, endotoxin stimulated a dose-related increase in both the synthesis and the secretion of IL-1 beta, which reached similar levels to those seen after in-vivo stimulation. Hypothalami obtained from animals stimulated with endotoxin in vivo did not, however, show any evidence of persistent stimulation of IL-1 beta production when subsequently cultured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Hagan
P
P
Division of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK.
Poole
S
S
Bristow
A F
AF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D009924:Organ Culture Techniques; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012762:Shigella dysenteriae
D004731:Endotoxins; D007375:Interleukin-1