|Myers, M. - DIV. ANIMAL RES.,FDA|
|Farrell, D. - DIV.ANIMAL RES.,FDA|
|Baker, J. - DIV THERAPEUTIC DRUGS,FDA|
|Cope, C. - DIV.ANIMAL RES., FDA|
Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 1, 1999
Publication Date: N/A
Interpretive Summary: Growing and finishing swine were challenged with endotoxin at either 2 or 20 mg/kg body weight. Both groups of animals are immunologically mature. However, the groups did not always respond the same immunologically, as far as the cytokines and metabolites measured in this study. Peak TNFa plasma levels were observed 1-2 hours post challenge in a dose-response relationship as measured by bioassay, returning to basal values by 4 hours post challenge. Maximal plasma interluekin-6 (IL-6) levels occurred 1-2 hours post challenge and remained elevated through 8 hours post challenge. In contrast to TNF, there was no dose response in IL-6 production, suggesting that IL-6 is very sensitive to endotoxin challenge and may not be a useful marker of infection or inflammation in swine. In contrast with the immunological findings, changes in plasma metabolites, such as urea nitrogen and free fatty acids, were strictly related to the physiological status of the animal and did not exhibit any dose-response relationship. These results suggest that a single age or metabolic status group of swine will not serve as a universal tool for how all swine respond to an endotoxin challenge.
Technical Abstract: Growing and finishing swine challenged with endotoxin at either 2or 20 mg/kg body weight produced tumor necrosis factor (TNF)a ina dose-response relationship as measured by bioassay. Peak TNFaplasma levels were observed 1-2 hours post challenge, returningto basal values by 4 hours post challenge. However, both an enzyme-linked immunosorbent assay specific for rswine TNFa and total human TNFa demonstrated no dose-response relationship Maximal plasma interluekin-6 levels occurred 1-2 hours postchallenge and remained elevated through 8 hours post challenge. There was no dose response. 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 dto metabolic status. Urea nitrogen levels were unchanged in growing swine whereas they were increased in finishing swine and remained elevated 24 hours post challenge. FFA levels in growing and finishing swine increased 3-6 hours post challenge. FFA levels returned to basal values for finishing swine 24 hours post challenge, but in growing swine remained elevated 24 hours postchallenge. Results demonstrate that endotoxin challenge of swine results in a pattern of changes that are dependent on both the dose of endotoxin used and the metabolic status/age of the animal.