Submitted to: American Society of Animal Science
Publication Type: Abstract only
Publication Acceptance Date: 3/31/2004
Publication Date: 4/1/2004
Citation: Elsasser, T.H., Kahl, S. 2004. Failure to downregulate tumor necrosis factor responses to repeated endotoxin challenge in cattle constitutes a pathophysiological relevant marker of risk for increased morbidity and mortality [abstract]. Journal of Animal Science 82(Suppl.1):179. Interpretive Summary:
Technical Abstract: The tolerance phenomenon is a progressive physiological downregulation of the cytokine cascade responses to repeated challenge with inflammatory stimuli like LPS necessary to attenuate the development of multiorgan failure that occurs from the formation of oxy-nitrogen free radicals and initiation of the tissue damage via the complement C9 membrane attack pathway (cMAP). Using repeated, graded doses of E. coli 055:B5 LPS, we have identified and characterized subpopulations of cattle who fail to develop tolerance to repeated LPS in their presentation of significantly greater changes in the immune response event-initiating proinflammatory cytokine TNF-' and corresponding indicators of increased morbidity and disease response. Crossbred beef heifers (n=32, av wht 323 kg) were injected twice in five days with LPS (0.8 µg/kg BW 0.75 ) with representative blood samples obtained for measurement of plasma TNF-' by RIA. The response index (TIND, TNF-a area response to the first challenge divided by the area response to the second challenge) for each heifer was ranked and outliers (tolerance failure heifers, n=6, TFH: PROC Univariate Z-score) identified and grouped and retested with a contemporary group of tolerant heifers (n=6,TH) at 9.46 µg/kg BW 0.75 LPS. TIND responses to LPS were highly repeatable across dose and correlated (P<0.02). Replenishment of lost body weight following LPS was delayed (P<0.02) in TFH vs TH). Plasma acute phase response protein marker (APRPM, serum amyloid-A, haptoglobin, P<0.01) concentration changes were greater and temporally prolonged after the repeated LPS challenge in TFH vs TH. Computer-assisted immunohistochemical quantification indicated an increased intensity of positive cMAP staining at 24 H post LPS in TFH vs TF (P<0.05). The data indicate that TNF-' and APRPM responses to repeated LPS challenge testing can identify animals at risk of greater morbidity response to disease vector challenge.