Neural circuits mediating circulating interleukin-1β-evoked fever in the absence of prostaglandin E2 production.
Neural circuits mediating circulating interleukin-1β-evoked fever in the absence of prostaglandin E2 production.
复制标题
在无前列腺素E2产生的情况下介导循环白细胞介素-1 β诱发发热的神经回路
DOI：
10.1016/j.bbi.2022.04.008
复制
发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
感染性疾病和炎性病症招募免疫系统以发起适当的急性反应，包括细胞因子的产生。细胞因子引起神经介导的反应以对抗病原体，例如热效应器的募集，从而增加体温并导致发热。研究表明，细胞因子白细胞介素-1 β（IL-1β）依赖于环氧合酶（考克斯）介导的前列腺素E2的产生，用于诱导引起发热的神经机制。然而，考克斯抑制剂不能消除IL-1β诱导的发热，因此表明外周给予IL-1β后，COX依赖性和COX非依赖性机制被招募用于升高体温。在本研究中，我们的目的是建立一个基础的神经回路控制COX非依赖性，炎症性发热，通过确定参与的大脑区域，是至关重要的控制交感神经流出到棕色脂肪组织（BAT）和皮肤血管。在麻醉大鼠中，用非选择性考克斯抑制剂吲哚美辛预处理不能阻止BAT产热或静脉注射IL-1β（2 μg/kg）诱导的皮肤血管收缩（CVC）。在有或没有用吲哚美辛预处理的情况下，IL-1β诱发的BAT产热和CVC需要在中缝苍白球喙部区域（rRPa）中的BAT和皮肤血管系统交感神经前运动神经元。此外，激活背内侧下丘脑（DMH）中的谷氨酸受体是COX非依赖性、IL-1β诱导的BAT产热所必需的。因此，我们的数据表明，COX非依赖性机制引起DMH和rRPa内神经元的激活，这足以触发和引起炎性发热。这些数据为阐明负责COX非依赖性、IL-1β引起的发热的脑回路提供了基础。
Infectious diseases and inflammatory conditions recruit the immune system to mount an appropriate acute response that includes the production of cytokines. Cytokines evoke neurally-mediated responses to fight pathogens, such as the recruitment of thermoeffectors, thereby increasing body temperature and leading to fever. Studies suggest that the cytokine interleukin-1β (IL-1β) depends upon cyclooxygenase (COX)-mediated prostaglandin E2 production for the induction of neural mechanisms to elicit fever. However, COX inhibitors do not eliminate IL-1β-induced fever, thus suggesting that COX-dependent and COX-independent mechanisms are recruited for increasing body temperature after peripheral administration of IL-1β. In the present study, we aimed to build a foundation for the neural circuit(s) controlling COX-independent, inflammatory fever by determining the involvement of brain areas that are critical for controlling the sympathetic outflow to brown adipose tissue (BAT) and the cutaneous vasculature. In anesthetized rats, pretreatment with indomethacin, a non-selective COX inhibitor, did not prevent BAT thermogenesis or cutaneous vasoconstriction (CVC) induced by intravenous IL-1β (2 μg/kg). BAT and cutaneous vasculature sympathetic premotor neurons in the rostral raphe pallidus area (rRPa) are required for IL-1β-evoked BAT thermogenesis and CVC, with or without pretreatment with indomethacin. Additionally, activation of glutamate receptors in the dorsomedial hypothalamus (DMH) is required for COX-independent, IL-1β-induced BAT thermogenesis. Therefore, our data suggests that COX-independent mechanisms elicit activation of neurons within the DMH and rRPa, which is sufficient to trigger and mount inflammatory fever. These data provide a foundation for elucidating the brain circuits responsible for COX-independent, IL-1β-elicited fevers.
登录
查看更多内容
DOI：
10.1016/s1036-7314(97)70414-4
发表时间：
1997-12-01
期刊：
Australian critical care : official journal of the Confederation of Australian Critical Care Nurses
影响因子：
--
作者：
Boyle, M;Hundy, S;Torda, T A
通讯作者：
Torda, T A
影响因子：
5.3
作者：
Ching, San;Zhang, Hao;Quan, Ning
通讯作者：
Quan, Ning
影响因子：
7.8
作者：
Dinarello CA;van der Meer JW
通讯作者：
van der Meer JW
影响因子：
6.7
作者：
de Souza, GEP;Cardoso, RA;Zampronio, AR
通讯作者：
Zampronio, AR
影响因子：
2.5
作者：
BANKS, WA;KASTIN, AJ;GUTIERREZ, EG
通讯作者：
GUTIERREZ, EG