Bodnar R J, Pasternak G W, Mann P E, Paul D, Warren R, Donner D B
Cotzias Laboratory of Neurooncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res. 1989 Nov 15;49(22):6280-4.
Human recombinant tumor necrosis factor (TNF) produces significant anorexia in the rat which persists for up to 24 h after a single dose (5 micrograms/325 g rat). Dose-response studies indicate similar potencies for TNF following central or peripheral administration. Brain 125I-TNF levels were more than 100-fold greater after intracerebroventricular than i.v. injection, whereas blood levels of radioactivity were quite similar following both routes of administration. Gel filtration chromatography and precipitation by trichloroacetic acid showed that the radioactive label which exited the central nervous system was associated with intact TNF. The rapid effusion of 125I-TNF from the central nervous system resulted in detection of similar levels of the cytokine in a number of important target tissues (skin, muscle, fat) relative to that detected after peripheral administration. After i.v. or intracerebroventricular administration, blood levels of TNF declined rapidly to nearly undetectable levels over 4 h. However, the anorexia induced by TNF was sustained, and feeding remained depressed between 6 and 24 h postadministration. These observations suggest that TNF produces its anorectic effects at peripheral sites, possibly through mediators.
重组人肿瘤坏死因子（TNF）可使大鼠出现明显的厌食症状，单次给药（5微克/325克大鼠）后，这种症状可持续长达24小时。剂量反应研究表明，中枢或外周给药后，TNF的效力相似。脑室内注射后，脑内125I-TNF水平比静脉注射高100多倍，而两种给药途径后血液中的放射性水平相当相似。凝胶过滤色谱法和三氯乙酸沉淀法显示，从中枢神经系统排出的放射性标记物与完整的TNF相关。125I-TNF从中枢神经系统的快速渗出导致在一些重要靶组织（皮肤、肌肉、脂肪）中检测到的细胞因子水平与外周给药后检测到的水平相似。静脉注射或脑室内注射后，TNF的血液水平在4小时内迅速下降至几乎无法检测的水平。然而，TNF诱导的厌食症状持续存在，给药后6至24小时进食仍受到抑制。这些观察结果表明，TNF可能通过介质在外周部位产生厌食作用。
