Prostaglandin E2 and bacterial lipopolysaccharide stimulate bioactive interleukin-1 release from rat hypothalamic explants.
While interleukin-1 (IL-1) is intimately involved in locally modulating the acute inflammatory response, it is also able to influence processes at remote sites, i.e., in an endocrine manner. While there is as yet little evidence that IL-1 can cross the blood-brain barrier, many effects such as fever, increased slow-wave sleep, anorexia and the modulation of neuroendocrine function suggest an action of circulating IL-1 at regulatory sites within the hypothalamus. However, there is accumulating evidence for IL-1 originating within the central nervous system (CNS), and it is currently unclear as to whether the neurally mediated manifestations of the acute inflammatory response are due to activation of central or peripheral (circulating) IL-1. In this study we have characterized the release of IL-1 from rat hypothalamic explants, and we have investigated the effects of putative modulators of IL-1 release, lipopolysaccharide (LPS) and the prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha). After 1 h of incubation, IL-1-like activity in hypothalamic supernatants ranged between 175 and 2,304 munits/mg of protein; this was substantially inhibited by the addition to the bioassay system of antibodies (1:200) against IL-1 alpha, but not against IL-1 beta. LPS and PGE2 significantly stimulated IL-1 release at 100 and 1 ng/ml respectively, whereas PGF2 alpha had no effect in the range of doses tested. It is therefore concluded that the control of hypothalamic IL-1 release may be investigated by means of acute rat hypothalamic explants.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Catholic University Medical School, Rome, Italy.
P
P
Navarra
G
G
Pozzoli
C
C
Becherucci
P
P
Preziosi
A B
AB
Grossman
L
L
Parente
D000818:Animals; D000906:Antibodies; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015237:Dinoprost; D015232:Dinoprostone