INTERLEUKIN-6 AS AN ENDOGENOUS PYROGEN - INDUCTION OF PROSTAGLANDIN-E2 IN BRAIN BUT NOT IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS
INTERLEUKIN-6 AS AN ENDOGENOUS PYROGEN - INDUCTION OF PROSTAGLANDIN-E2 IN BRAIN BUT NOT IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS
复制标题
DOI：
10.1016/0006-8993(91)90622-3
复制
发表时间：
1991-10-25
期刊：
影响因子：
2.9
通讯作者：
COCEANI, F
中科院分区：
文献类型：
--
作者：
DINARELLO, CA;CANNON, JG;COCEANI, F
由内源性和外源性热原引起的发热通常可以通过环氧合酶抑制剂来预防;内源性热原刺激大脑体温调节中心内或附近的前列腺素E2（PGE 2）。细胞因子，白细胞介素-1（IL-1）和肿瘤坏死因子（TNF），是两种在发热期间刺激脑PGE 2形成的致热原，也增加体外人单核细胞中PGE 2的合成。在本研究中，我们研究了白细胞介素-6（IL-6）是否以类似于IL-1和TNF的方式刺激PGE 2的形成。测试了重组人IL-6的糖基化和非糖基化形式。静脉注射到家兔体内后，糖基化IL-6比非糖基化形式更具致热原性，并且当同时给予IL-6和IL-1时，没有证据表明产生发热的协同作用。IL-6发热通过预先给予环氧合酶抑制剂布洛芬而被阻断。IL-6也通过全身或脑室内途径在猫中产生热原。然而，在这两个物种中，IL-6的有效性低于IL-1-β。当给猫脑室注射IL-6时，脑脊液中PGE 2水平的增加与体温的升高平行。在后一方面，IL-6模拟IL-1-β;然而，0.15-15 μ g/ml的IL-6在体外不增加单核细胞PGE 2的产生，而IL-1-β在100 ng/ml诱导PGE 2增加20-30倍。这些结果表明，IL-6，类似于IL-1和TNF，通过脑PGE 2合成的快速增加引起发热，但与IL-1不同，IL-6未观察到单核细胞中PGE 2的刺激。
Fever induced by endogenous as well as exogenous pyrogens is often prevented by cyclooxygenase inhibitors; endogenous pyrogens stimulate prostaglandin E2 (PGE2) in or near the thermoregulatory centers of the brain. The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), are two pyrogens which stimulate brain PGE2 formation during fever and also increase PGE2 synthesis in human mononuclear cells in vitro. In the present study, we examined whether interleukin-6 (IL-6) stimulates PGE2 formation in a manner similar to IL-1 and TNF. Both glycosylated and non-glycosylated forms of recombinant human IL-6 were tested. Following intravenous injection into rabbits, the glycosylated IL-6 was more pyrogenic than the non-glycosylated form and there was no evidence of synergy in the production of fever when IL-6 and IL-1 were given simultaneously. IL-6 fever was blocked by prior administration of the cyclooxygenase inhibitor ibuprofen. IL-6 was also pyrogenic in the cat by either the systemic or the intraventricular route. However, in both species, IL-6 was less effective than IL-1-beta. When given intraventricularly to cats, IL-6 produced an increase in PGE2 levels of the cerebrospinal fluid in parallel with the rise in body temperature. In the latter respect, IL-6 imitated IL-1-beta; however, IL-6 from 0.15-15-mu-g/ml did not increase mononuclear cell PGE2 production in vitro whereas IL-1-beta-induced 20-30-fold increases in PGE2 at 100 ng/ml. These results suggest that IL-6, similar to IL-1 and TNF, causes fever via the rapid increase in brain PGE2 synthesis but unlike IL-1, stimulation of PGE2 in mononuclear cells was not observed by IL-6.