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Prior Stressor Exposure Sensitizes LPS-Induced Cytokine Production

https://doi.org/10.1006/brbi.2001.0638Get rights and content

Abstract

Exposure to stressors often alters the subsequent responsiveness of many systems. The present study tested whether prior exposure to inescapable tailshock (IS) alters the interleukin (IL)-1β, tumor necrosis factor (TNF)-α, or IL-6 response to an injection of bacterial endotoxin (lipopolysaccharide; LPS). Rats were exposed to IS or remained as home cage controls (HCC); 24 h later animals were injected i.p. with either 10 μg/kg LPS or equilvolume sterile saline. IS significantly increased plasma TNF-α, IL-1β, and pituitary, hypothalamus, hippocampus, cerebellum IL-1β 1 h, but not 2 h, after LPS, compared to controls. Additional animals were injected with LPS or saline 4, 10, or 21 days after exposure to IS and tail vein blood was collected and assayed for IL-1β. An enhanced plasma IL-1β response occurred 4 days after IS, but was gone by 10 days. These results suggest that exposure to IS sensitizes the innate immune response to LPS by resulting in either a larger or a more rapid induction of proinflammatory cytokines.

References (79)

  • E. Goujon et al.

    Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice

    Brain Behav. Immun.

    (1995)
  • B.L. Hart

    Biological basis of the behavior of sick animals

    Neurosci. Biobehav. Rev.

    (1988)
  • R.L. Hauger et al.

    CRF receptor regulation and sensitization of ACTH responses to acute ether stress during chronic intermittent immobilization stress

    Brain Res.

    (1990)
  • S. Kent et al.

    Sickness behavior as a new target for drug development

    Trends Pharmacol. Sci.

    (1992)
  • S. Kent et al.

    Reduction in food and water intake induced by microinjection of interleukin-1 beta in the ventromedial hypothalamus of the rat

    Physiol. Behav.

    (1994)
  • M. Konarska et al.

    Sensitization of sympathetic–adrenal medullary responses to a novel stressor in chronically stressed laboratory rats

    Physiol. Behav.

    (1989)
  • J. Lachuer et al.

    The habituation of brainstem catecholaminergic groups to chronic daily restraint stress is stress specific like that of the hypothalamo–pituitary–adrenal axis

    Brain Res.

    (1994)
  • S. Laye et al.

    Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice

    Brain. Res. Mol. Brain Res.

    (1994)
  • L.G. LeMay et al.

    The effects of psychological stress on plasma interleukin-6 activity in rats

    Physiol. Behav.

    (1990)
  • L.G. LeMay et al.

    In vivo evidence that the rise in plasma IL 6 following injection of a fever-inducing dose of LPS is mediated by IL 1 beta

    Cytokine

    (1990)
  • M. Leyton et al.

    Preexposure to foot-shock sensitizes the locomotor response to subsequent systemic morphine and intra-nucleus accumbens amphetamine

    Pharmacol. Biochem. Behav.

    (1990)
  • Z. Merali et al.

    Effects of interleukin-1 beta and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: A regional microdialysis study

    Brain Res.

    (1997)
  • B.H. Natelson et al.

    Effect of stressor intensity on habituation of the adrenocortical stress response

    Physiol. Behav.

    (1988)
  • P.V. Piazza et al.

    The role of stress in drug self-administration

    Trends Pharmacol. Sci.

    (1998)
  • D.L. Pitman et al.

    Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: Chronic stress and habituation

    Physiol. Behav.

    (1988)
  • N. Quan et al.

    Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide

    J. Neuroimmunol.

    (1994)
  • N.J. Rothwell et al.

    Pharmacology of interleukin-1 actions in the brain

    Adv. Pharmacol.

    (1994)
  • B. Schobitz et al.

    Gene expression and function of interleukin 1, interleukin 6 and tumor necrosis factor in the brain

    Prog. Neurobiol.

    (1994)
  • T. Wilckens et al.

    Glucocorticoids and immune function: Unknown dimensions and new frontiers

    Immunol Today

    (1997)
  • H. Anisman et al.

    Anhedonic and anxiogenic effects of cytokine exposure

    Adv. Exp. Med. Biol.

    (1999)
  • S.M. Antelman et al.

    Interchangeability of stress and amphetamine in sensitization

    Science

    (1980)
  • J.E. Blalock

    The immune system as a sensory organ

    J. Immunol.

    (1984)
  • J. Borrell et al.

    Sound stimulation and its effects on the pituitary–adrenocortical function and brain catecholamines in rats

    Neuroendocrinology

    (1980)
  • L.S. Brady et al.

    Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain

    J. Neurosci.

    (1994)
  • C. Chancellor-Freeland et al.

    Substance P and stress-induced changes in macrophages

    Ann. N. Y. Acad. Sci.

    (1995)
  • E. Corsini et al.

    Human brain endothelial cells and astrocytes produce IL-1 beta but not IL-10

    Scand. J. Immunol.

    (1996)
  • M.J. Dascombe et al.

    Pyrogenic and thermogenic effects of interleukin 1 beta in the rat

    Am. J. Physiol.

    (1989)
  • T. Deak et al.

    Evidence that brief stress may induce the acute phase response in rats

    Behav. Neurosci.

    (1997)
  • F.S. Dhabhar et al.

    Stress-induced enhancement of antigen-specific cell-mediated immunity

    J. Immunol.

    (1996)
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      LPS, as compared to the other stimulating agents, induced high levels of TNF, IL-6, IL-1β and IL-10 in both LCL patients and healthy controls. This is in line with previous report showed LPS induce TNF, IL-6, IL-1β in human phagocytic cells [42,43]. Poly I:C, as compared to the other stimuli, induced higher levels of IL-12p70.

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    To whom correspondence should be addressed at Department of Psychology, University of Colorado, Boulder, CO 80309-0345. Fax: (303) 492-2967. E-mail: [email protected].

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