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-induced fever is dependent on dose
1 Department of Psychology and Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado 80309; and 2 Department of Psychology, University of Virginia, Charlottesville, Virginia 22904
It has been suggested that proinflammatory
cytokines communicate to the brain via a neural pathway involving
activation of vagal afferents by interleukin-1
(IL-1
), in
addition to blood-borne routes. In support, subdiaphragmatic vagotomy
blocks IL-1
-induced, brain-mediated responses such as fever.
However, vagotomy has also been reported to be ineffective. Neural
signaling would be expected to be especially important at low doses of
cytokine, when local actions could occur, but only very small
quantities of cytokine would become systemic. Here, we examined core
body temperature after intraperitoneal injections of three doses of recombinat human IL-1
(rh-IL-1
). Subdiaphragmatic vagotomy
completely blocked the fever produced by 0.1 µg/kg, only partially
blocked the fever produced by 0.5 µg/kg, and had no effect at all on
the fever that followed 1.0 µg/kg rh-IL-1
. Blood levels of
rh-IL-1
did not become greater than normal basal levels of
endogenous rat IL-
until the 0.5-µg/kg dose nor was IL-1
induced in the pituitary until this dose. These results suggest that
low doses of intraperitoneal IL-1
induce fever via a vagal route and
that dose may account for some of the discrepancies in the literature.
cytokines; vagotomy; immune-to-brain communication; rat
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