Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo.
Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo.
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DOI：
10.1084/jem.184.3.883
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发表时间：
1996-09-01
期刊：
影响因子：
--
通讯作者：
Isakson PC
中科院分区：
文献类型：
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作者：
Portanova JP;Zhang Y;Anderson GD;Hauser SD;Masferrer JL;Seibert K;Gregory SA;Isakson PC
使用中和抗前列腺素E2单克隆抗体2B 5在体内评价前列腺素E2（PGE 2）在炎症症状发展和细胞因子产生中的作用。在角叉菜胶诱导的爪炎症中，用2B 5预处理大鼠基本上防止了受影响爪中组织水肿和痛觉过敏的发展。该抗体显示结合炎症部位产生的大部分PGE 2。在抗炎药诱导的关节炎中，对关节炎大鼠进行2B 5治疗性给药可显著逆转受累爪的水肿。抗PGE 2治疗还降低了爪中IL-6 RNA和血清IL-6蛋白的水平，而没有改变相同组织中肿瘤坏死因子RNA的水平。在每种模型中，2B 5的抗抑郁疗效与非甾体类抗抑郁药吲哚美辛（indomethacin）的疗效没有区别，后者阻断了所有PG的产生。这些结果表明，PGE 2在炎症部位的组织水肿、痛觉过敏和IL-6产生中起主要作用，并且它们表明PGE 2合成或活性的选择性药理学调节可提供减轻炎性疾病症状的有用手段。
The role of prostaglandin E2 (PGE2) in the development of inflammatory symptoms and cytokine production was evaluated in vivo using a neutralizing anti-PGE2 monoclonal antibody 2B5. In carrageenan-induced paw inflammation, pretreatment of rats with 2B5 substantially prevented the development of tissue edema and hyperalgesia in affected paws. The antibody was shown to bind the majority of PGE2 produced at the inflammatory site. In adjuvant-induced arthritis, the therapeutic administration of 2B5 to arthritic rats substantially reversed edema in affected paws. Anti-PGE2 treatment also reduced paw levels of IL-6 RNA and serum IL-6 protein without modifying tumor necrosis factor RNA levels in the same tissue. In each model, the antiinflammatory efficacy of 2B5 was indistinguishable from that of the nonsteroidal antiinflammatory drug indomethacin, which blocked the production of all PGs. These results indicate that PGE2 plays a major role in tissue edema, hyperalgesia, and IL-6 production at sites of inflammation, and they suggest that selective pharmacologic modulation of PGE2 synthesis or activity may provide a useful means of mitigating the symptoms of inflammatory disease.