Induction of the acute-phase cytokine, hepatocyte-stimulating factor/interleukin 6, in the circulation of horses treated with endotoxin

Robert J. MacKay From the Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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 BVSc, PhD
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Guy D. Lester From the Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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 BVMS, PhD

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Summary

Because hepatocyte-stimulating factor/interleukin 6 (il-6) is the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating il-6 activity was monitored in 4 adult horses for 72 hours after iv administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin—1,000, 30, 1, and 0 ng/kg of body weight. Plasma il-6 activity was quantified as the ability to promote growth of the il-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 ± 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P < 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kg dosage of endotoxin, peak plasma il-6 activity (10,128 ± 4,096 and 1,555 ± 1,326 U/ml, respectively) was observed for 3 hours. The il-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma il-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.

Summary

Because hepatocyte-stimulating factor/interleukin 6 (il-6) is the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating il-6 activity was monitored in 4 adult horses for 72 hours after iv administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin—1,000, 30, 1, and 0 ng/kg of body weight. Plasma il-6 activity was quantified as the ability to promote growth of the il-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 ± 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P < 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kg dosage of endotoxin, peak plasma il-6 activity (10,128 ± 4,096 and 1,555 ± 1,326 U/ml, respectively) was observed for 3 hours. The il-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma il-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.

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