Role of hypothalamic interleukin-1beta in fever induced by cecal ligation and puncture in rats.
Bacterial endotoxin induces fever by causing the release of interleukin (IL)-1beta into the circulation or the brain. IL-1beta is believed to mediate fever via triggering the production and/or release of IL-6 in the hypothalamus. The present study examined whether IL-1beta and IL-6 in the hypothalamus of the rat are also involved in fever during bacterial sepsis caused by cecal ligation and puncture (CLP). CLP induces fever for 2 days. Polyclonal rabbit antibody against rat IL-1beta (anti-IL-1beta, 2 microg/microl) or control rabbit IgG (2 microg/microl) was unilaterally microinjected into the hypothalamus of rats immediately after or 24 h after CLP or sham-CLP surgery. Anti-IL-1beta injected 24 h after CLP (when fever was already present) or sham-CLP surgery did not affect fever. Microinjection of anti-IL-1beta into the hypothalamus immediately after surgery caused a significant decrease in body temperature during the night after CLP surgery and a 48% reduction of fever on the following day. Although blood plasma levels of IL-6 were significantly elevated 1.5, 6, 24, and 48 h after CLP surgery, there were no differences in IL-6 concentrations in the extracellular fluid of the anterior hypothalamus (collected by push-pull perfusion). These data suggest that fever due to bacterial sepsis is initiated by IL-1beta within the hypothalamus, and this febrile response, unlike endotoxin-induced fever, is not accompanied by elevation in the hypothalamic concentration of IL-6.
Gourine
A V
AV
Lovelace Respiratory Research Institute, Inhalation Toxicology Laboratory, Albuquerque, New Mexico 87185, USA.
Rudolph
K
K
Tesfaigzi
J
J
Kluger
M J
MJ
D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000503:physiopathology; D002432:Cecum / Q000382:microbiology / Q000601:surgery*; D005334:Fever / Q000209:etiology / Q000503:physiopathology*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000032:analysis; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D007700:Kinetics; D008026:Ligation; D008297:Male; D008845:Microinjections; D011677:Punctures; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*; D014018:Tissue Distribution
D007074:Immunoglobulin G; D007375:Interleukin-1; D011994:Recombinant Proteins