Assessment of the ovine acute phase response and hepatic gene expression in response to Escherichia coli endotoxin

• Published in: Veterinary Immunology and Immunopathology 2006-09, Vol.113 (1), p.113-124
• Main Authors: Kabaroff, Leah C., Rodriguez, Alexander, Quinton, Margaret, Boermans, Herman, Karrow, Niel A.
• Format: Article
• Language: English
• Subjects: acute phase proteins; Acute-Phase Reaction - immunology; Acute-Phase Reaction - veterinary; Acute-phase response; Animals; bacterial toxins; biopsy; Biopsy - veterinary; blood chemistry; body temperature; cortisol; cytokines; Cytokines - genetics; Cytokines - immunology; dose response; Dose-Response Relationship, Immunologic; endotoxins; Escherichia coli; Escherichia coli - immunology; Escherichia coli Infections - immunology; Escherichia coli Infections - microbiology; Escherichia coli Infections - veterinary; Female; fever; gene expression; Gene Expression - drug effects; Hepatic gene expression; hepatocytes; Hydrocortisone - blood; Hypothalamic–pituitary–adrenal axis; Hypothalamo-Hypophyseal System - immunology; immune response; inflammation; interleukin-6; Interleukin-6 - blood; Lipopolysaccharide; Lipopolysaccharide Receptors - genetics; Lipopolysaccharide Receptors - immunology; lipopolysaccharides; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; liver; Liver - immunology; monocytes; Ovine; Pituitary-Adrenal System - immunology; protein synthesis; Reverse Transcriptase Polymerase Chain Reaction; Sheep; Sheep Diseases - immunology; Sheep Diseases - microbiology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0165-2427; 1873-2534; 1365-2567
• DOI: 10.1016/j.vetimm.2006.04.003

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-α, IL-1β, macrophage migration inhibitory factor, 11-β-hydroxysteroid dehydrogenase (HSD), and tachykinin precursor 1 hepatic genes was dependent on both the dose and the kinetics of the response to LPS.