Waage A
Cell Research Laboratory, Institute of Cancer Research University of Trondheim, Norway.
Clin Immunol Immunopathol. 1987 Dec;45(3):348-55. doi: 10.1016/0090-1229(87)90087-0.
The production and clearance of tumor necrosis factor (TNF) in relation to endotoxinemia was studied by the injection of lipopolysaccharide (LPS) in rats. TNF was released into the circulation as a burst when the serum concentration of LPS was rapidly or gradually increased. The maximum concentration of TNF in serum was attained 60 to 90 min after the injection of LPS. TNF was eliminated from the serum according to a first-order kinetics; the half-life was calculated to be 27 +/- 7 min. No additional release of TNF could be evoked by a persistent high level of LPS. When two LPS injections were given within 3 days, the peak concentration of TNF detected after the second injection was 15% of the concentration detected after the first injection. The results indicate that if TNF is a mediator of septic shock, its role is restricted to the initial phase after the appearance of endotoxin in the circulation. Treatment of the rats with dexamethasone (0.5-2.0 micrograms/g) reduced the LPS-induced peak concentrations of TNF in serum by 70-90%. Maximal suppression of the TNF release was observed when dexamethasone was given 5 hr or more prior to LPS, but was gradually lost at shorter intervals.
通过给大鼠注射脂多糖（LPS），研究了肿瘤坏死因子（TNF）的产生和清除与内毒素血症的关系。当LPS的血清浓度快速或逐渐升高时，TNF会以突发形式释放到循环中。注射LPS后60至90分钟，血清中TNF达到最大浓度。TNF从血清中按照一级动力学消除；计算出半衰期为27±7分钟。持续高水平的LPS不会引起TNF的额外释放。当在3天内进行两次LPS注射时，第二次注射后检测到的TNF峰值浓度是第一次注射后检测到浓度的15%。结果表明，如果TNF是脓毒性休克的介质，其作用仅限于循环中出现内毒素后的初始阶段。用地塞米松（0.5 - 2.0微克/克）治疗大鼠可使LPS诱导的血清中TNF峰值浓度降低70 - 90%。当地塞米松在LPS注射前5小时或更长时间给药时，观察到对TNF释放的最大抑制，但在较短时间间隔时逐渐消失。
