Inflammation ＆ Fever

将角叉菜胶注射到大鼠的后爪中引起局部炎症以及包括发热的全身症状。然而，这种炎症引起的发热的机制尚不清楚。为了阐明这一机制，我们分析了PGE_2，引发发热，环氧合酶-2（考克斯-2）和微粒体的PGE_2合成所需的，都与这个实验模型。给予考克斯-2酶抑制剂可抑制角叉菜胶引起的发热，并伴有脑脊液（CSF）中PGE_2的升高和脑内皮细胞中考克斯-2的表达。当在5个时间点测量时，即，注射角叉菜胶后1.5、3、6、12、24 h，水肿、发热、PGE_2和考克斯-2整合虹膜张力呈相似的时程，直至6 h，所有这些指标均达到峰值。术后发热和PGE_2迅速恢复至基线水平，而考克斯-2积分强度和水肿体积仅部分下降。结果提示，脑内皮细胞表达考克斯-2和mPGES，导致PGE_2的产生，从而引起外周炎症引起发热，并提示在发热恢复期，脑组织中PGE_2的表达可能与脑组织中PGE_2的表达有关。即使在考克斯-2和mPGES存在的情况下，也存在一种抑制PGE_2形成的未知机制。结论：脑内皮细胞表达考克斯-2和mPGES通过产生PGE_2在炎症性发热中起重要作用。

Injection of carrageenan into the hind paw of rats evokes localized inflammation as well as systemic symptoms including fever. However, the mechanism of this inflammation-induced fever is not known. To clarify this mechanism, we analyzed prostagrandin E_2 (PGE_2), which triggers fever, cyclooxygenase-2 (COX-2) and microsomal prostagrandin E synthase (mPGES), both of which are required for PGE_2 biosynthesis, with this experimental model. Fever evoked by carageenan was suppressed by administration of an enzyme inhibitor for COX-2 and was accompanied with a rise in PGE_2 in the cerebrospinal fluid (CSF), and expression of COX-2 in the brain endothelial cells. When measured at 5 time points, i.e., 1.5, 3, 6, 12, f 24 he after carageen an injection, edema, fever, PGE_2 and COX-2-integrated-iritensiry followed a similar time course until 6 hours, at which time all of these measures were at their peaks. After that, fever and PGE_2 returned to the baselines promptly whereas the COX-2-integrated-intensity and edema volume decreased only partially. Unlike these, mPGES integrated-intensity rose more slowly than the above elements to its peak at 12 hr and the level was almost the same at 24 hr. These results imply that expression of COX-2 and mPGES in brain endothelial cells lead to the production of PGE_2 resulting in fever caused by peripheral inflammation and also suggests that, in the recovery phase of fever, there is a recruitment of unidentified mechanism that suppresses PGE_2 formation even in the presence of COX-2 and mPGES. In conclusion, COX-2 and mPGES expression in brain endotherial cells play an essential role in the inflammation-induced fever by producing PGE_2.