Assessment of the ovine acute phase response and hepatic gene expression in response to Escherichia coli endotoxin Leah C. Kabaroff a , Alexander Rodriguez b , Margaret Quinton a , Herman Boermans c , Niel A. Karrow a, * a Department of Animal and Poultry Science, University of Guelph, Guelph, Ont., Canada N1G 2W1 b Department of Clinical Studies, University of Guelph, Guelph, Ont., Canada N1G 2W1 c Department of Biomedical Sciences, University of Guelph, Guelph, Ont., Canada, N1G 2W1 Received 30 September 2005; accepted 20 April 2006 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-a, IL-1b, macrophage migration inhibitory factor, 11-b-hydroxysteroid dehydrogenase (HSD), and tachykinin precursor 1 hepatic genes was dependent on both the dose and the kinetics of the response to LPS. # 2006 Elsevier B.V. All rights reserved. Keywords: Acute-phase response; Hepatic gene expression; Lipopolysaccharide; Hypothalamic–pituitary–adrenal axis; Ovine 1. Introduction During gram-negative bacterial infections, LPS, a pathogen associated molecular pattern (PAMP) is released into the surrounding microenvironment du- ring host-mediated bacteriolysis. Lipopolysaccharide www.elsevier.com/locate/vetimm Veterinary Immunology and Immunopathology 113 (2006) 113–124 * Corresponding author. Tel.: +1 519 824 4120x53646; fax: +1 519 767 0573. E-mail address: nkarrow@uoguelph.ca (N.A. Karrow). 0165-2427/$ – see front matter # 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2006.04.003