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The Journal of Neuroscience, March 15, 1998, 18(6):2239-2246
Exposure to Acute Stress Induces Brain
Interleukin-1 Protein in the Rat
Kien T.
Nguyen1,
Terrence
Deak1,
Stephanie
M.
Owens1,
Tadahiko
Kohno3,
Monika
Fleshner2,
Linda R.
Watkins1, and
Steven F.
Maier1
Departments of 1 Psychology and
2 Kinesiology, University of Colorado at Boulder, Boulder,
Colorado 80309, and 3 Amgen-Boulder Inc., Boulder,
Colorado 80301
Peripheral immune stimulation such as that provided by
lipopolysaccharide (LPS) has been reported to increase brain levels of
IL-1 mRNA, immunoreactivity, and bioactivity. Stressors produce many
of the same neural and endocrine responses as those that follow LPS,
but the impact of stressors on brain interleukin-1 (IL-1) has not
been systematically explored. An ELISA designed to detect IL-1 was
used to measure levels of IL-1 protein in rat brain. Brain IL-1
was explored after exposure to inescapable shock (IS; 100 1.6 mA tail
shocks for 5 sec each) and LPS (1 mg/kg) as a positive control. Rats
were killed either immediately or 2, 7, 24, or 48 hr after IS. Brains
were dissected into hypothalamus, hippocampus, cerebellum, posterior
cortex, and nucleus tractus solitarius regions. LPS produced widespread
increases in brain IL-1, but IS did not. Adrenal glucocorticoids are
known to suppress IL-1 production in both the periphery and brain.
Thus, it was possible that the stressor did provide stimulus input to
the brain IL-1 system(s), but that the production of IL-1 protein
was suppressed by the rapid and prolonged high levels of
glucocorticoids produced by IS. To test this possibility rats were
adrenalectomized or given sham surgery, with half of the
adrenalectomized rats receiving corticosterone replacement to maintain
basal corticosterone levels. IS produced large increases in brain
IL-1 protein in the adrenalectomized subjects 2 hr after stress,
whether basal corticosterone levels had been maintained. Thus
elimination of the stress-induced rise in corticosterone unmasked a
robust and widespread increase in brain IL-1.
Key words:
interleukin-1; stress; brain; glucocorticoids; protein; rat
Copyright © 1998 Society for Neuroscience 0270-6474/98/1862239-08$05.00/0
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