title: Assessment of the ovine acute phase response and hepatic gene expression in response to Escherichia coli endotoxin.
abstract: Lipopolysaccharide (LPS), a bacterial membrane endotoxin, induces a systemic inflammatory response (IFR) through the activation of blood monocytes and hepatic kupffer cells. These cells secrete pro-inflammatory cytokines, which subsequently activate the hypothalamic-pituitary-adrenal axis (HPAA) to release cortisol, an anti-inflammatory hormone that regulates the IFR and subsequent immune response (IR). The intent of this study was to characterize the acute phase response in female sheep challenged systemically with a range of doses of Escherichia coli endotoxin. Yearling ewes were challenged with an i.v. bolus dose of LPS (0, 200, 400, 600 ng/kg BW) and the acute phase response assessed by measuring serum interleukin (IL)-6 and cortisol concentrations, and the febrile response over time. A follow-up liver biopsy study was performed to determine kinetic differences in the expression of eight candidate hepatic genes between LPS dose groups using real-time RT-PCR. The initial time trail did not follow a linear dose response relationship with respect to the febrile and HPAA response to LPS challenge. Serum IL-6 concentrations increased in the two highest treatment groups but did not correlate with the observed febrile and HPAA response. The expression of Toll-like receptor 4, CD14, IL-6, tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, 11-beta-hydroxysteroid dehydrogenase (HSD), and tachykinin precursor 1 hepatic genes was dependent on both the dose and the kinetics of the response to LPS.
authors.affiliation: Department of Animal and Poultry Science, University of Guelph, Guelph, Ont., Canada N1G 2W1.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Kabaroff
authors.forename: Alexander
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Margaret
authors.initials: M
authors.lastname: Quinton
authors.forename: Herman
authors.initials: H
authors.lastname: Boermans
authors.forename: Niel A
authors.initials: NA
authors.lastname: Karrow
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology / Q000662:veterinary*; D000818:Animals; D001706:Biopsy / Q000662:veterinary; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008099:Liver / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology / Q000382:microbiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C439524:TNF protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone