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

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.