Macrophage inflammatory protein-1 beta (MIP-1 beta) produced endogenously in brain during E-coli fever in rats
Macrophage inflammatory protein-1 beta (MIP-1 beta) produced endogenously in brain during E-coli fever in rats
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DOI：
10.1111/j.1460-9568.1996.tb01225.x
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发表时间：
1996-02-01
影响因子：
3.4
通讯作者：
Armengol, JA
中科院分区：
文献类型：
--
作者：
Minano, FJ;FernandezAlonso, A;Armengol, JA
巨噬细胞炎性蛋白-1（MIP-1）引起高热，不依赖于前列腺素机制，现在被认为在细菌热原的防御反应中起重要作用。本研究的目的有两个方面：（i）确定这种细胞因子MIP-1 β的有效双联体是否实际上是在脑中响应于致热剂量的大肠杆菌脂多糖而产生的，以及（ii）确定这种细胞因子在脑中合成的解剖部位。在不受限制的大鼠腹腔内注射脂多糖产生高热后，在与发热有关的两个脑区（终板血管器（OVLT）和下丘脑前部视前区（AH/POA））中发现了MIP-1 β免疫反应性。直接将山羊抗小鼠MIP-1 β抗体（抗MIP-1 β）微量注射到AH/POA中可显著抑制大鼠对脂多糖的发热反应。此外，在注射脂多糖后180分钟给予抗MIP-1 β作为解热剂并逆转由内毒素诱导的发热。抗MIP-1 β或对照免疫球蛋白G抗体显微注射到下丘脑之前立即腹腔注射对照盐水没有改变大鼠的温度。综上所述，本结果表明MIP-1 β在脑中响应于细菌内毒素而产生。根据MIP-1 β诱导发热的早期数据，这些观察结果进一步支持了这样的假设，即内源性合成的MIP-1 β通过作用于大脑的热敏细胞而在发热的诱发中充当中介因子。
Macrophage inflammatory protein-1 (MIP-1) evokes an intense fever, independent of a prostaglandin mechanism, and is now thought to play an important role in the defence response to bacterial pyrogens. The purpose of this study was 2-fold: (i) to determine whether the potent doublet of this cytokine, MIP-1 beta, is actually produced in the brain in response to a pyrogenic dose of a lipopolysaccharide of Escherichia coli and (ii) to determine the anatomical site of synthesis of this cytokine in the brain. Following the intense fever produced by intraperitoneal administration of lipopolysaccharide in the unrestrained rat, MIP-1 beta immunoreactivity was identified post mortem in two regions of the brain implicated in fever: the organum vasculosum laminae terminalis (OVLT) and the anterior hypothalamic, preoptic area (AH/POA). Microinjection of goat anti-mouse MIP-1 beta antibody (anti-MIP-1 beta) directly into the AH/POA markedly suppressed fever in rats in response to lipopolysaccharide. Further, anti-MIP-1 beta administered 180 min after the injection of lipopolysaccharide acted as an antipyretic and reversed the fever induced by the endotoxin. Anti-MIP-1 beta or control immunoglobulin G antibody microinjected into the hypothalamus immediately before the intraperitoneal injection of the control saline did not alter the temperature of the rats. Taken together, the present results demonstrate that MIP-1 beta is produced in the brain in response to a bacterial endotoxin. These observations, in the light of earlier data on fever induced by MIP-1 beta, further support the hypothesis that endogenously synthesized MIP-1 beta acts as an intermediary factor in the evocation of fever by acting on the thermosensitive cells of the brain.