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in fever induced by
cecal ligation and puncture in rats
Lovelace Respiratory Research Institute, Inhalation Toxicology Laboratory, Albuquerque, New Mexico 87185
Bacterial endotoxin induces
fever by causing the release of interleukin (IL)-1
into the
circulation or the brain. IL-1
is believed to mediate fever via
triggering the production and/or release of IL-6 in the
hypothalamus. The present study examined whether IL-1
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-1
(anti-IL-1
, 2 µg/µl) or control rabbit IgG (2 µg/µl) was
unilaterally microinjected into the hypothalamus of rats immediately
after or 24 h after CLP or sham-CLP surgery. Anti-IL-1
injected 24 h
after CLP (when fever was already present) or sham-CLP surgery did not
affect fever. Microinjection of anti-IL-1
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-1
within the hypothalamus, and this febrile response, unlike
endotoxin-induced fever, is not accompanied by elevation in the
hypothalamic concentration of IL-6.
cytokines; endotoxin; push-pull perfusion; temperature regulation
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