The Mechanism Of Bai-Hu-Tang (BHT) Decoction On Fever Induced By Endotoxin (ET)

Purpose:The aim of this study is to investigate the antifebrile effect of Bai-Hu-Tang (BHT),a Traditional Chinese Medicinal(TCM) prescription.Material and method:The animals used in this study were male New Zealand white rabbits weighing 2.0-2.5 kg.They were housed in a room maintained at 21±1℃with a 12 h light-dark cycle.Food and water were available ad libitum.The i.v.injection of ET was made into the marginal ear vein.The other threes groups of rabbits were orally administered with 0.9%saline solution,BHT and ibuprofen.Then the blood samples were collected in tubes from the ear center artery of rabbits. After sampling the blood,the rabbits were killed and the hypothalamus was rapidly removed and frozen at-80℃for subsequent interleukin-1 beta(IL-1β) and tumor necrosis factor alpha(TNF-α) activity assays.The concentrations of IL-1βand TNF-αin serum and hypothalamus were assayed using a commercially available rabbit IL-1βand TNF-αELISA kits following the manufacturer's instructions.Results:1.Injection of ET(200 ng/kg) induced a biphasic fever,the first peak of the biphasic fever occurred at 1 h after injection and the second peak occurred at 3 h after injection.In contrast,BHT treatment group resulted in a significant fall in body temperature in both peaks(P＜0.05),and treatment with ibuprofen attenuated the first peak of the fever(P＜0.05),but did not result in a significant fall in the second peak of the fever(P＞0.05).Control animals administered only saline failed to show any change in body temperature.2.At time 1 h,the levers of IL-1βand TNF-αall had significant difference between control and ET groups(P＜0.05).Both BHT and ibuprofen treatment groups resulted in a significant fall in the concentrations of IL-1βand TNF-αin serum compared with the group that only treatment with ET(P＜0.05).BHT did not fall the concentration of IL-1βin the hypothalamus compared with the ET group(P＞0.05),but ibuprofen reduced the concentration of IL-1βin the hypothalamus compared with the ET group(P＜0.05).In addition,the concentration of TNF-αin hypothalamus of BHT group had a remarkable reduce compared with that of ET group(P＜0.05),but ibuprofen group had a similar lever with ET group(P＞0.05).Ibuprofen could fall both the concentrations of IL-1β,TNF-αin serum and the lever of IL-1βin hypothalamus to reduce the first peak of the body temperature in ET induced fever,but BHT reduced the concentrations of IL-1β,TNF-αin serum and the concentration of TNF-αin hypothalamus to fall the first peak of the fever.3.At time 3 h,the concentrations of IL-1βboth in hypothalamus and serum of BHT group were significantly low compared with the concentrations of ET group (P＜0.05).There was no significant change on the concentration of TNF-αin serum between ET and control groups(P＞0.05),but the concentration of TNF-αin hypothalamus had significant difference between ET and control groups(P＜0.05),while BHT group represented the remarkable control on the rising concentration of TNF-αin hypothalamus(P＜0.05).Ibuprofen treatment group resulted in a significant fall in the concentrations of IL-1βboth in serum and hypothalamus compared with the group that only treatment with ET(P＜0.05), but there was no remarkable difference on the concentration of TNF-αin hypothalamus compared with it in ET group(P＞0.05). Conclusion:1.The main findings of this study were that treatments with the crude extract of BHT could remarkably reduce the biphasic fever that was elicited by ET. Tbuprofen,a specific cyclooxygenase inhibitor,reduced the first phase of biphasic fever clearly,but did not affect the late peak of fever.2.The increased concentrations of IL-1β,TNF-αin serum of the rabbits might be the part mechanism in the first peak of biphasic fever that was elicited by ET.And the remarkably increased concentration of TNF-αin hypothalamus might play an important role in the second peak of biphasic fever.3.BHT reduced the concentrations of IL-1β,TNF-αin serum to control the febrile responses at time 1 h;and at time 3 h,the concentration of TNF-αin hypothalamus were significant lower in BHT group than that of in ET group, and that were maybe the part mechanism of BHT in reducing the body temperature induced by injecting ET.