Coceani Flavio, Akarsu Eyup S
Division of Neurosciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Ann N Y Acad Sci. 1998 Sep 29;856:76-82. doi: 10.1111/j.1749-6632.1998.tb08315.x.
Prostaglandin E2 (PGE2) is recognized as a key intermediate in the sequence of events leading to fever. Normally undetectable or barely detectable in brain, it rises selectively on exposure to an infectious noxa and the attendant generation of pyrogenic cytokines outside and, in the case of interleukin (IL)-6, inside the brain. The mechanism by which pyrogens in the circulation promote the appearance of PGE2 within the confines of brain is not clear, and it is not known how PGE2 activation is selective with IL-6 being induced in brain. We have found that the cerebral microvasculature is not suitable as a source of PGE2 in response to blood-borne pyrogens. In addition, we show that IL-6 differs from other pyrogens in being able to stimulate specifically PGE2 synthesis. Nevertheless, brain-derived IL-6 does not appear to be necessary for PGE2 activation and the attendant fever. We conclude that signal-transducing mechanisms operating across the blood-brain barrier are most critical for the development of the febrile response to a systemic noxa.
前列腺素E2（PGE2）被认为是导致发热的一系列事件中的关键中间体。在大脑中通常无法检测到或仅能勉强检测到，在接触感染性损伤因素以及随之在脑外产生致热细胞因子（就白细胞介素（IL）-6而言，还包括脑内产生）时，它会选择性升高。循环中的致热原促进脑内PGE2出现的机制尚不清楚，也不清楚PGE2激活如何在脑内诱导IL-6时具有选择性。我们发现，脑微血管系统不适合作为对血源性感热原产生PGE2的来源。此外，我们表明IL-6与其他致热原不同，它能够特异性刺激PGE2合成。然而，脑源性IL-6似乎对于PGE2激活及随之而来的发热并非必需。我们得出结论，跨越血脑屏障运行的信号转导机制对于全身性损伤因素引起的发热反应的发展最为关键。
