title: Exposure to acute stress induces brain interleukin-1beta protein in the rat.
abstract: Peripheral immune stimulation such as that provided by lipopolysaccharide (LPS) has been reported to increase brain levels of IL-1beta 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-1beta (IL-1beta) has not been systematically explored. An ELISA designed to detect IL-1beta was used to measure levels of IL-1beta protein in rat brain. Brain IL-1beta 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-1beta, but IS did not. Adrenal glucocorticoids are known to suppress IL-1beta production in both the periphery and brain. Thus, it was possible that the stressor did provide stimulus input to the brain IL-1beta system(s), but that the production of IL-1beta 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-1beta 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-1beta.
authors.affiliation: Department of Psychology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: T
authors.initials: T
authors.lastname: Deak
authors.forename: S M
authors.initials: SM
authors.lastname: Owens
authors.forename: T
authors.initials: T
authors.lastname: Kohno
authors.forename: M
authors.initials: M
authors.lastname: Fleshner
authors.forename: L R
authors.initials: LR
authors.lastname: Watkins
authors.forename: S F
authors.initials: SF
authors.lastname: Maier
mesh_terms: D000208:Acute Disease; D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D004597:Electroshock; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D013623:Tail
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D003345:Corticosterone