Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta.
Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta.
复制标题
Cyclooxygenase-2 介导小鼠对 IL-1β 的发热反应。
DOI：
10.1016/s0006-8993(01)02707-x
复制
发表时间：
2001
期刊：
影响因子：
2.9
通讯作者：
Blatteis,CM
中科院分区：
文献类型：
--
作者：
Li,S;Ballou,LR;Morham,SG;Blatteis,CM
各种证据表明，环加氧酶(COX)-2是外源性热原脂多糖（LPS）诱导的发热的调节剂。因此，用特异性COX-2抑制剂治疗可抑制发热反应，而不影响基础体温（Tc）。此外，COX-2基因消融小鼠不能对腹腔注射（i.p.）产生发热反应。而他们的cox -1缺陷对应物产生的发烧与野生型（WT）对照没有什么不同。为了将COX-2在lps诱导的发热中明显的关键作用扩展到内源性热原引起的发热，我们研究了COX-1-和COX-2先天缺陷小鼠对重组小鼠（rm）白细胞介素(IL)-1β的热反应。我们还评估了一种选择性COX-1抑制剂SC-560和两种选择性COX-2抑制剂尼美利德（NIM）和二甲基呋喃酮（DFU）对LPS和rmIL-1β的发热反应的影响。最后，我们验证了动物对PGE2， i.c.v的反应的完整性。i.c.v和rmIL-1β在WT和COX-1敲除小鼠中引起类似的发热，但没有引起COX-2无效突变体的Tcs升高。SC-560不影响LPS引起的WT小鼠发热，但NIM和DFU分别使其发热减弱和消失，而DFU则将LPS引起的rmIL-1β转化为Tcfall。在WT和COX基因敲除小鼠中，对icv pge2的反应没有差异。因此，这些结果进一步支持了pge2响应热原的产生严重依赖于COX-2表达的观点。
Various lines of evidence have implicated cyclooxygenase (COX)-2 as a modulator of the fever induced by the exogenous pyrogen lipopolysaccharide (LPS). Thus, treatment with specific inhibitors of COX-2 suppresses the febrile response without affecting basal body (core) temperature (Tc). Furthermore, COX-2 gene-ablated mice are unable to develop a febrile response to intraperitoneal (i.p.) LPS, whereas their COX-1-deficient counterparts produce fevers not different from their wild-type (WT) controls. To extend the apparently critical role of COX-2 for LPS-induced fevers to fevers produced by endogenous pyrogens, we studied the thermal responses of COX-1- and COX-2 congenitally deficient mice to i.p. and intracerebroventricular (i.c.v.) injections of recombinant murine (rm) interleukin (IL)-1β. We also assessed the effects of one selective COX-1 inhibitor, SC-560, and two selective COX-2 inhibitors, nimesulide (NIM) and dimethylfuranone (DFU), on the febrile responses of WT and COX-1−/−mice to LPS and rmIL-1β, i.p. Finally, we verified the integrity of the animals’ responses to PGE2, i.c.v. I.p. and i.c.v. rmIL-1β induced similar fevers in WT and COX-1 knockout mice, but provoked no rise in the Tcs of COX-2 null mutants. The fever produced in WT mice by i.p. LPS was not affected by SC-560, but it was attenuated and abolished by NIM and DFU, respectively, while that caused by i.p. rmIL-1β was converted into a Tcfall by DFU. There were no differences in the responses to i.c.v. PGE2among the WT and COX knockout mice. These results, therefore, further support the notion that the production of PGE2in response to pyrogens is critically dependent on COX-2 expression.