Attenuated fever in rats during late pregnancy is linked to suppressed interieukin-6 production after localized inflammation with turpentine
Attenuated fever in rats during late pregnancy is linked to suppressed interieukin-6 production after localized inflammation with turpentine
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DOI：
10.1113/jphysiol.2007.132829
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发表时间：
2007-08-15
影响因子：
5.5
通讯作者：
Luheshi, Giamal N.
中科院分区：
文献类型：
--
作者：
Aguilar-Valles, Argel;Poole, Stephen;Luheshi, Giamal N.
妊娠晚期对病原体的发烧反应减弱是几种哺乳动物物种中的一种现象，尽管机制尚不完全清楚，但与前列腺素 E-2 (PGE(2)) 合成减少有关。在 PGE2 的上游，有证据表明抗炎细胞因子如白细胞介素 1 受体拮抗剂 (IL-1ra) 可能发挥重要作用。在本研究中，我们探讨了促炎细胞因子在妊娠晚期的作用，特别是白细胞介素 6 (IL-6)，它是发烧的重要循环介质。松节油 (TURP) 是一种非常有效的热原和 IL-6 激活剂，在妊娠第 18 天 (GD 18) 或年龄匹配的非妊娠 (NP) 雌性对照大鼠的后肢肌肉中注射。正如预期的那样，TURP 注射在 NP 动物中引起了高度显着的发烧，在注射后 11 小时达到峰值，并持续超过 24 小时。伴随着循环IL-6水平的显着升高，这与下丘脑中PGE2合成酶表达的变化相关。与此形成鲜明对比的是，GD 18 只动物完全没有 TURP 引起的发热，其体温没有偏离基础值。 IL-6 浓度没有变化以及 PGE2 合成酶表达的显着减弱也反映了反应的缺乏，这与 SOCS3（IL-6 活性的下丘脑标志物）表达的抑制相关。与 GD 18 时循环 IL-6 水平的变化相反，IL-1ra 被诱导至与 NP 雌性相当的水平，表明这种抗炎细胞因子对 TURP 发热反应的影响至多是最小的。这些数据进一步证实了 IL-6 在发烧产生中的重要性，并提供了证据表明它可能是妊娠晚期发烧反应减弱的关键组成部分。
An attenuated fever response to pathogens during late pregnancy is a phenomenon that has been described in several mammalian species, and although mechanisms are not completely understood, decreased prostaglandin E-2 (PGE(2)) synthesis has been implicated. Upstream of PGE2, there is evidence to suggest that anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1ra) could play a significant role. In the present study we addressed the role of pro-inflammatory cytokines during late pregnancy, specifically interleukin-6 (IL-6), an important circulating mediator in fever. Turpentine oil (TURP), a very potent pyrogen and activator of IL-6, was injected into the hind-limb muscle of rats at the 18th day of pregnancy (GD 18) or in non-pregnant (NP) age-matched female controls. As expected, TURP injection induced a highly significant fever in the NP animals, which peaked 11 h post-injection and lasted for over 24 h. This was accompanied by a significant rise in circulating IL-6 levels, which correlated with changes in PGE2 synthesizing enzymes expression in the hypothalamus. In complete contrast, TURP-induced fever was totally absent in GD 18 animals whose body temperature did not deviate from basal values. The lack of response was additionally reflected by the absence of change in IL-6 concentration and by the significant attenuation of PGE2 synthesizing enzymes expression, which correlated with the suppressed expression of SOCS3, a hypothalamic marker of IL-6 activity. Contrary to the changes in circulating IL-6 levels at GD 18, IL-1ra was induced to levels comparable to those of NP females, suggesting that the influence of this anti-inflammatory cytokine on the fever response to TURP is at best minimal. These data further confirm the importance of IL-6 in fever generation and provide evidence that it may be a key component of the attenuated fever response in late pregnancy.