THE ROLE OF HMGB-1 AS CYTOKINE IN INFECTION

柑橘类黄酮橙皮苷(HES)可抑制脂多糖(LPS)诱导的显色反应。小鼠在脂多糖攻击前给予贺斯可显著降低肿瘤坏死因子α的产生，且呈剂量依赖关系。HES治疗前3h(Ip)。感染108CFU鼠伤寒沙门氏菌可使小鼠从致死性休克中解救出来，与脂多糖无反应小鼠相似。HES可显著降低小鼠肝、脾内细菌数量和血浆内毒素水平。此外，贺斯还能显著降低血浆中肿瘤坏死因子-α的水平，减少肝脏中的细胞凋亡，并使感染引起的凝血酶原时间和血小板数量等凝血因子的激活状态正常化。腹膜腔内(Ip)感染10^8CFU Salmo…更多的Nella typhimurium Aroa在脂多糖(LPS)应答的小鼠中引起致死性休克，而不是无应答的小鼠。感染前3h给予1 mg柚皮苷可保护小鼠免受致死性休克，与无反应的小鼠相似。柚皮苷的保护作用具有时间和剂量依赖性。用柚皮苷治疗不仅能显著减少脾和肝脏中的细菌数量，而且还能降低血浆内毒素水平。此外，柚皮苷显著抑制肿瘤坏死因子-α，并使感染引起的凝血酶原时间、纤维蛋白原浓度和血小板数量等凝血因子的激活状态正常化。研究了具有内毒素结合活性的抗生素多粘菌素B(PLB)对感染性内毒素休克小鼠的保护作用。用减毒鼠伤寒沙门氏菌Aroa株的10 8个集落形成单位感染ddy小鼠，可致致死性内毒素休克。感染后1小时用PLB治疗(P.I.)显著降低了死亡率和肝脏中的细菌数量。另外，用PLB治疗1h，P.I.导致早期血浆内毒素水平一过性升高，随后逐渐下降。虽然血浆sCD14和高迁移率族蛋白-1(HMGB-1)水平随着感染的进展而升高，但PLB治疗1h后，血浆sCD14和HMGB-1水平的升高被下调。而抗CD14单抗处理3h和6h均不能阻断致死性休克。有趣的是，给药后6小时P.I.没有显示任何保护性活动，这表明存在采取有效公共部门行动的时间窗口。较少

Lipopolysaccharide (LPS)-elicited chromogenic Limulus reaction was suppressed by pretreating LPS with a citrus flavonoid hesperidin (HES). Administration of HES to mice before LPS challenge significantly reduced tumor necrosis factor (TNF)-α production in a dose-dependent manner. Treatment of HES 3 h before intraperitoneal (i.p.) infection with 108 CFU Salmonella typhimurium aroA resulted in rescue from lethal shock as similar to LPS-nonresponder mice. Not only bacterial numbers in livers and spleens but also plasma LPS levels significantly decreased by pretreating with HES. In addition, HES markedly suppressed plasma TNF-a levels, decreased the number of apoptotic cells in livers and normalized the activated states of blood coagulation factors such as prothrombin time and platelet numbers caused by infection.The protective effect of Citrus flavanone naringin was demonstrated in an endotoxin shock model based on Salmonella infection. Intraperitoneal (i.p.) infection with 10^8 CFU Salmo … More nella typhimurium aroA caused lethal shock in lipopolysaccharide (LPS)-responder but not -nonresponder mice. Administration of 1 mg naringin 3 h before infection resulted in protection from lethal shock, similar to LPS-nonresponder mice. The protective effect of naringin was time- and dose-dependent. Treatment with naringin resulted not only in a significant decrease in bacterial numbers in spleens and livers, but also a decrease in plasma LPS levels. In addition, naringin markedly suppressed TNF-a and normalized the activated states of blood coagulation factors such as prothrombin time, fibrinogen concentration and platelet numbers caused by infection. Interestingly, treatment with naringin suppressed high levels of soluble CD14 and high mobility group-1 molecule caused by infection.The protective effects of an antibiotic polymyxin B (PLB), having lipopolysaccharide (LPS)-binding activity, on infection-induced endotoxin shock in mice were investigated. Infection with 10^8 colony forming units of an attenuated Salmonella typhimurium aroA strain caused lethal endotoxin shock to ddY mice. Treatment with PLB 1 h post infection (p.i.) resulted in significant reduction of mortality and bacterial numbers in livers. In addition, treatment with PLB 1 h p.i. resulted in a transient increase at the early stage and gradual decline in plasma LPS levels. Although plasma levels of sCD14 and high mobility group box chromosomal protein-1 (HMGB-1) increased according with progression of infection, increases in plasma levels of sCD14 and HMGB-1 were downregulated by treatment with PLB 1 h p.i. However, the lethal shock was not blocked by treatment with anti-CD14 monoclonal antibody at 3 h and 6 h p.i. Interestingly, administration of PLB 6 h p.i. did not show any protective activities, indicating that a time window for effective PLB action is present. Less