title: Prior stressor exposure sensitizes LPS-induced cytokine production.
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)-1beta, tumor necrosis factor (TNF)-alpha, 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 microg/kg LPS or equilvolume sterile saline. IS significantly increased plasma TNF-alpha, IL-1beta, and pituitary, hypothalamus, hippocampus, cerebellum IL-1beta 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-1beta. An enhanced plasma IL-1beta 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.
authors.affiliation: Department of Psychology and Center for Neuroscience, University of Colorado, Boulder, Colorado 80309-0345, USA. jjohnson@psych.colorado.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Johnson
authors.forename: Kevin A
authors.initials: KA
authors.lastname: O'Connor
authors.forename: Terrence
authors.initials: T
authors.lastname: Deak
authors.forename: Matt
authors.initials: M
authors.lastname: Stark
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D004597:Electroshock; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000139:chemically induced / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha