Somnogenic effects of rabbit and recombinant human interferons in rabbits.

Somnogenic effects of rabbit and recombinant human interferons in rabbits.
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兔子和重组人干扰素对兔子的催眠作用。

DOI:
10.1152/ajpregu.1994.267.1.r53
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发表时间:
1994
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Krueger,JM
Krueger,JM
中科院分区:
--
文献类型:
--
作者:
Kimura,M;Majde,JA;Toth,LA;Opp,MR;Krueger,JM

文献摘要

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干扰素(IFN)是一种具有多种中枢神经系统活动的抗病毒细胞因子。干扰素治疗与嗜睡有关,病毒感染期间表达的干扰素可能与这些感染相关的过度睡眠有关。大多数病毒都能刺激干扰素-α和干扰素-β的产生。虽然大剂量的人干扰素-α2对兔有催眠作用,但物种特异性的干扰素对兔睡眠的影响尚未被记录在案。我们比较了兔来源的干扰素与重组人(Rh)干扰素-α和干扰素-β的催眠和抗病毒作用。脑室注射重组人干扰素-αA/D、兔干扰素-α/β和兔参比干扰素可剂量依赖性地诱导非快动眼睡眠和发热。然而,兔干扰素诱导睡眠所需的剂量远低于人干扰素。兔干扰素和人干扰素的体外抗病毒作用均显著降低。热处理后,兔干扰素和重组人干扰素-αA/D的体内活性显著降低。然而,重组人干扰素-β在热处理后仍具有促进睡眠的作用,这表明微生物污染物是其催眠和致热活性的原因。我们得出结论:干扰素-α具有催眠作用。
Interferons (IFNs) are antiviral cytokines that possess several central nervous system activities. IFN therapy is associated with sleepiness, and the IFNs expressed during viral infection may be involved in the excess sleep associated with these infections. Most viruses stimulate the production of both IFN-alpha and IFN-beta. Although large doses of human IFN-alpha 2 are somnogenic in rabbits, the effects of species-specific IFNs on sleep in the rabbit have not been documented. We compared the somnogenic and antiviral effects of IFNs derived from rabbits to the effects of recombinant human (rh) IFN-alpha and IFN-beta. When injected intracerebroventricularly, rhIFN-alpha A/D, rabbit IFN-alpha/beta, and rabbit reference IFN induced non-rapid-eye-movement sleep and fever in a dose-dependent manner. However, the doses of rabbit IFNs required to induce sleep were much lower than those of human IFNs. Heat treatment of both rabbit IFNs and human IFNs greatly reduced their in vitro antiviral effects. The in vivo activities of rabbit IFNs and rhIFN-alpha A/D were significantly attenuated after heat treatment. However, rhIFN-beta retained its sleep-promoting action after heat treatment, suggesting that microbial contaminants were responsible for its somnogenic and pyrogenic activities. We conclude that IFN-alpha is somnogenic.