促肾上腺皮质激素释放激素参与由一种独特的预先形成的致热因子（PFPF）诱导的发热过程。

Involvement of CRH in fever induced by a distinct pre-formed pyrogenic factor (PFPF).

作者信息

Zampronio A R, Melo M C, Hopkins S J, Souza G E

机构信息

Lab. Farmacologia, Fac. Ciências Farmacêuticas de Ribeirão Preto, SP, Brasil.

出版信息

Inflamm Res. 2000 Sep;49(9):473-9. doi: 10.1007/s000110050619.

DOI:10.1007/s000110050619

PMID:11071122

Abstract

OBJECTIVE

This study investigated the role of corticotrophin-releasing hormone (CRH) in mediating the fever induced by a novel pre-formed pyrogenic factor (PFPF), using a CRF antagonist in vivo and evaluating the capacity of PFPF to stimulate CRH release from the hypothalamus in vitro.

MATERIALS AND METHODS

Male Wistar rats were used. The PFPF, induced following brief incubation of rat peritoneal macrophages with LPS and retained on 10 or 20 kDa MW cut-off membranes, was injected intracerebroventricularly. Fever was monitored using a rectal probe. Hypothalamus tissue was incubated with PFPF to establish its ability to induce CRH release. The CRH was measured by ELISA.

RESULTS

PFPF induced a dose-dependent fever that was abolished by boiling or pronase treatment. Whereas both dexamethasone and indomethacin were effective in reducing interleukin- (IL) 1beta-induced fever, only dexamethasone abolished the fever induced by PFPF. The CRH antagonist, a-helical CRH9-41, abolished the fever induced by synthetic CRH, IL-8 and PFPF but not tumour necrosis factor-a (TNF-alpha). Like IL-1, PFPF was able to induce the release of CRH from rat hypothalamic tissue in vitro.

CONCLUSIONS

These results suggest that the fever induced by PFPF depends on CRH release but not prostaglandin synthesis.

摘要

目的

本研究使用促肾上腺皮质激素释放激素（CRH）拮抗剂在体内研究CRH在介导一种新型预成型致热因子（PFPF）诱导的发热中的作用，并在体外评估PFPF刺激下丘脑释放CRH的能力。

材料与方法

使用雄性Wistar大鼠。将大鼠腹膜巨噬细胞与脂多糖（LPS）短暂孵育后诱导产生并保留在截留分子量为10或20 kDa的膜上的PFPF，经脑室内注射。使用直肠探头监测发热情况。将下丘脑组织与PFPF一起孵育，以确定其诱导CRH释放的能力。通过酶联免疫吸附测定法（ELISA）测量CRH。

结果

PFPF诱导剂量依赖性发热，煮沸或经链霉蛋白酶处理后发热消失。地塞米松和吲哚美辛均能有效降低白细胞介素-（IL）1β诱导的发热，但只有地塞米松能消除PFPF诱导的发热。CRH拮抗剂α-螺旋CRH9-41能消除合成CRH、IL-8和PFPF诱导的发热，但不能消除肿瘤坏死因子-α（TNF-α）诱导的发热。与IL-1一样，PFPF在体外能够诱导大鼠下丘脑组织释放CRH。