Tumor necrosis factor as a potential mediator of acute metabolic and hormonal responses to endotoxemia in calves

Dale C. Kenison From the Ruminant Nutrition Laboratory and Zoonotic Diseases Laboratory, Livestock and Poultry Science Institute, USDA, Agricultural Research Service, Beltsville, MD 20705.

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Theodore H. Elsasser From the Ruminant Nutrition Laboratory and Zoonotic Diseases Laboratory, Livestock and Poultry Science Institute, USDA, Agricultural Research Service, Beltsville, MD 20705.

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Ronald Fayer From the Ruminant Nutrition Laboratory and Zoonotic Diseases Laboratory, Livestock and Poultry Science Institute, USDA, Agricultural Research Service, Beltsville, MD 20705.

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Summary

The effects of coliform endotoxin (e) and recombinant bovine tumor necrosis factor α (tnf) were compared with respect to clinical signs of disease and changes in plasma metabolite and pituitary and pancreatic hormone concentrations in calves. In addition, changes in plasma tnf concentration during each challenge exposure were quantitated by use of radioimmunoassay. Healthy Holstein bull calves with mean body weight of 90 kg were each given, in order, on different days, saline solution (5.0 ml, iv, day 1, n = 4), e (type 055:B5, 1.0 μg/kg of body weight iv, day 2, n = 4) and tnf (5.0 μg/kg iv, day 9, n = 3). Jugular venous blood samples, rectal temperature reading, and pcv were obtained at hourly intervals before (2 hours) and after challenge exposure. The pcv increased (P < 0.05) after e and tnf administrations for the first 5 hours, then returned to normal in calves given E, but decreased and remained low in calves given tnf through 24 hours. Plasma triglyceride and nonesterified free fatty acids concentrations were increased through 10 hours (P < 0.05) after e administration, whereas triglyceride and nonesterified free fatty acids concentrations were not significantly affected by tnf administration. Increase in blood glucose concentration at 1 hour after administration of e and tnf was followed by prolonged hypoglycemia that lasted through 6 hours. Changes in plasma insulin concentration paralleled the observed changes in glucose concentration, initially increased at 2 hours after e and tnf (P < 0.05) administrations, but then tended to decrease below control values thereafter. Plasma growth hormone and luteinizing hormone concentrations decreased after e and tnf administrations to almost nondetectable values through 4 hours after dosing, returning to normal values by 8 hours. The data indicate similarities in physiologic response of calves to e and tnf and suggest a role for acute production of tnf as a mediator of e responses.

Summary

The effects of coliform endotoxin (e) and recombinant bovine tumor necrosis factor α (tnf) were compared with respect to clinical signs of disease and changes in plasma metabolite and pituitary and pancreatic hormone concentrations in calves. In addition, changes in plasma tnf concentration during each challenge exposure were quantitated by use of radioimmunoassay. Healthy Holstein bull calves with mean body weight of 90 kg were each given, in order, on different days, saline solution (5.0 ml, iv, day 1, n = 4), e (type 055:B5, 1.0 μg/kg of body weight iv, day 2, n = 4) and tnf (5.0 μg/kg iv, day 9, n = 3). Jugular venous blood samples, rectal temperature reading, and pcv were obtained at hourly intervals before (2 hours) and after challenge exposure. The pcv increased (P < 0.05) after e and tnf administrations for the first 5 hours, then returned to normal in calves given E, but decreased and remained low in calves given tnf through 24 hours. Plasma triglyceride and nonesterified free fatty acids concentrations were increased through 10 hours (P < 0.05) after e administration, whereas triglyceride and nonesterified free fatty acids concentrations were not significantly affected by tnf administration. Increase in blood glucose concentration at 1 hour after administration of e and tnf was followed by prolonged hypoglycemia that lasted through 6 hours. Changes in plasma insulin concentration paralleled the observed changes in glucose concentration, initially increased at 2 hours after e and tnf (P < 0.05) administrations, but then tended to decrease below control values thereafter. Plasma growth hormone and luteinizing hormone concentrations decreased after e and tnf administrations to almost nondetectable values through 4 hours after dosing, returning to normal values by 8 hours. The data indicate similarities in physiologic response of calves to e and tnf and suggest a role for acute production of tnf as a mediator of e responses.

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