Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 21, 2004
Publication Date: June 1, 2005
Citation: Elsasser, T.H., Blum, J.W., Kahl, S. 2005. Characterization of calves exhibiting a novel inheritable TNF-a hyperresponsiveness to endotoxin: associations with increased pathophysiological complications. Journal of Applied Physiology. 98(6):2045-55.
Interpretive Summary: The stresses associated with infection and disease significantly affect many aspects of the economics of cattle production as well as the quality of product available to consumers. An animal's response to stress is played out in two parts: one part related to the onset of the responses to immune system-perceived challenges and another part wherein normal functions are reestablished in homeostasis. We have observed over several breeding seasons that there exist among populations of Bos Taurus cattle, individuals amounting to only 10 to 15 percent of the herd, who not only respond themselves overtly more severe than herd mates, but also the offspring of these cattle overtly respond as well. Using a well controlled and characterized low-level immune challenge of bacterial endotoxin challenge, we have established a test that can provide evidence that a certain animal may be at greater risk of severe response to a disease challenge and at greater risk of producing a calf with these same tendencies. Our double challenge test indicates that these overtly responding animals, herein termed 'hyper-responders', take significantly longer to fully recover from a low-level immune challenge and require more care to return to the herd. The study indicates that a major source of stress in a herd mad be accountable for with a minor number of animals. The early identification of disease-susceptible animals will help to provide management tools to improve animal welfare.
A subpopulation of calves from several populations, herein termed "hyper-responders" (HPR), was identified and defined by the patterns of plasma TNF-a concentrations that developed following two challenges with endotoxin (LPS, 0.8 mg E. coli 055:B5 LPS/kg0.75 live body weight) separated by 5 days. The principle characteristic of HPR-calves was associated with a failure to develop tolerance to the repeated LPS challenge that was evident in the magnitude of the TNF-a concentrations and prolonged severity of pathological sequellae. To test whether in vitro challenge of peripheral blood mononuclear cells (PBMNs) with a TNF-secretagogue could predict a potential for an animal to be HPR in vivo, PBMNs were isolated from the blood of 25 calves, plated and cultured for 4 hours, and challenged subsequently with either LPS (50 mg/ml) or phorbol myristate acetate (PMA, 100 ng/ml) for 4 additional hours. Media TNF-a concentrations were ranked from lowest to highest by calf; calves with highest and lowest media TNF concentrations (n=6/group) were selected for the two in vivo LPS challenges. Although calves failing to develop LPS tolerance were identified on the basis of excessive in vivo plasma TNF-a concentrations responses, in vitro PBMN TNF-a responses to the LPS and PMA secretagogues did not predict the magnitude of plasma TNF response and thus the HPR attribute in vivo Intentional breeding to obtain calves from bulls and/or cows documented as HPR resulted in offspring displaying the HPR character when similarly tested with LPS in vivo. Feed intake, clinical serology and hematology profiles, and acute phase response protein responses of HPR calves following LPS were significantly different from those of calves displaying tolerance. These results suggest that the pattern of plasma TNF-a changes that evolve from a low-level double LPS challenge effectively reveal the presence of a genetic potential for animals to display excessive or prolonged pathological response to endotoxin-related stress and compromised prognosis for recovery.