title: Challenge differentially affects cytokine production and metabolic status of growing and finishing swine.
abstract: Growing (35 kg body weight) and finishing (85 kg body weight) swine challenged with endotoxin (Escherichia coli O55:B5) at a dose of either 2 or 20 microg/kg produced tumor necrosis factor (TNF)alpha in a dose-response relationship as measured by bioassay. Peak TNFalpha plasma levels were observed 1-2 hr post-challenge, returning to basal values 4 hr post-challenge. However, both an enzyme-linked immunosorbent assay specific for swine TNFalpha and total human TNFalpha demonstrated no dose-response relationship; peak plasma levels of immunoreactive TNFalpha were also observed 1-2 hr post-challenge. Maximal plasma interleukin-6 levels occurred 1-2 hr post-challenge and remained elevated through 8 hr post-challenge; there was no effect of lipopolysaccharide dose or metabolic status. Although the metabolic status of the animals also affected glucose levels, with growing animals exhibiting greater sensitivity compared with finishing animals, endotoxin-induced decreases in blood glucose levels were primarily dose-dependent. In contrast, changes in plasma urea nitrogen and free fatty acid (FFA) levels were strictly related to the metabolic status. Urea nitrogen levels were unchanged in growing swine, whereas they were increased in finishing swine and remained elevated 24 hr post-challenge. FFA levels in growing and finishing swine increased 3-6 hr post-challenge. FFA levels returned to basal values for finishing swine 24 hr post challenge, but in growing swine remained elevated 24 hr post-challenge. Plasma aspartate transaminase levels were increased through 24 hr post-challenge; animals given a dose of 20 microg/kg exhibited the greatest increase. Similarly, swine challenged with a dose of 20 microg/kg also exhibited the greatest increase in levels of conjugated bilirubin; there was no effect on unconjugated (free) bilirubin. These results demonstrate that endotoxin challenge of swine result in a pattern of changes that are dependent on both the dose of endotoxin used and the metabolic status of the animal examined.
authors.affiliation: Division of Animal Research, US FDA, Center for Veterinary Medicine, Laurel, MD 20708, USA. mmyers@bangate.fda.gov
authors.forename: M J
authors.initials: MJ
authors.lastname: Myers
authors.forename: D E
authors.initials: DE
authors.lastname: Farrell
authors.forename: J D
authors.initials: JD
authors.lastname: Baker
authors.forename: C V
authors.initials: CV
authors.lastname: Cope
authors.forename: C M
authors.initials: CM
authors.lastname: Evock-Clover
authors.forename: N C
authors.initials: NC
authors.lastname: Steele
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine / Q000254:growth & development / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha