SYNERGY BETWEEN TUMOR-NECROSIS-FACTOR CT AND INTERLEUKIN-1 IN THE INDUCTION OF SICKNESS BEHAVIOR IN MICE
SYNERGY BETWEEN TUMOR-NECROSIS-FACTOR CT AND INTERLEUKIN-1 IN THE INDUCTION OF SICKNESS BEHAVIOR IN MICE
复制标题
DOI：
10.1016/0306-4530(94)90009-4
复制
发表时间：
1994-01-01
影响因子：
3.7
通讯作者：
DANTZER, R
中科院分区：
文献类型：
--
作者：
BLUTHE, RM;PAWLOWSKI, M;DANTZER, R
与白介素1一样，重组人肿瘤坏死因子α(TNFα)被发现以剂量和时间依赖的方式减少小鼠的社会探索并诱导体重减轻。本研究旨在研究这两种细胞因子之间的相互作用。小鼠ip阈值下剂量的肿瘤坏死因子α(2.5mU/只)和白介素1β(50 ng/只)。注射肿瘤坏死因子和白介素1后2、4h，小鼠的社会探索能力下降，但体重无明显变化。同时脑室注射阈值以下剂量的肿瘤坏死因子α(90 ng/只)和白介素1β(100 pg/只)。在注射两种细胞因子后1.5和3h，社会探索减少，体重减轻6h。为了检测IL-1受体拮抗剂(IL-1ra，1.8 mg/只，icv)对小鼠中枢诱导IL-1的可能性，给小鼠注射90 ng的TNF-α。IL-1ra可拮抗肿瘤坏死因子α对小鼠行为的抑制作用，但对该细胞因子诱导的体重减轻无影响。这些结果表明，肿瘤坏死因子α诱导的行为改变是由内源性释放的IL-1介导的，而代谢改变依赖于其他细胞因子的释放。
Like interleukin-1, recombinant human tumor necrosis factor alpha (TNF alpha) has been found to decrease social exploration and induce weight loss in mice in a dose and time-dependent manner. The present study was carried out to study the interaction between these two cytokines. Mice were injected IP with subthreshold doses of TNF alpha (2.5 mu g/mouse) and IL-1 beta (50 ng/mouse). Social exploration was decreased 2 and 4 h after injection of TNF and IL-1, but body weight was not affected. Subthreshold doses of TNF alpha (90 ng/mouse) and IL-1 beta (100 pg/mouse) were also injected intracerebroventricularly (ICV). Social exploration was decreased 1.5 and 3 h after injections of the two cytokines and body weight was decreased for 6 h. To test the possibility of central induction of IL-1 by TNF alpha, mice pretreated with IL-1 receptor antagonist (IL-1ra, 1.8 mu g/mouse, ICV) were injected with 90 ng TNF alpha. Pretreatment with IL-1ra antagonized the depressive effect of TNF alpha on behavior, but had no effect on weight loss induced by this cytokine. These results suggest that TNF alpha-induced behavioral alterations are mediated by endogenously released IL-1, whereas metabolic changes are dependent on the release of other cytokines.