Hyperresponsive febrile reactions to interleukin (IL) 1α and IL-1β, and altered brain cytokine mRNA and serum cytokine levels, in IL-1β-deficient mice

Hyperresponsive febrile reactions to interleukin (IL) 1α and IL-1β, and altered brain cytokine mRNA and serum cytokine levels, in IL-1β-deficient mice
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IL-1β 缺陷小鼠对白介素 (IL) 1α 和 IL-1β 的高反应性发热反应,以及脑细胞因子 mRNA 和血清细胞因子水平的改变

DOI:
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发表时间:
1997
期刊:
影响因子:
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通讯作者:
T. Bártfai
T. Bártfai
中科院分区:
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文献类型:
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作者:
K. Alheim;Z. Chai;G. Fantuzzi;H. Hasanvan;D. Malinowsky;E. D. Santo;P. Ghezzi;C. Dinarello;T. Bártfai

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IL-1β是一种内源性热原,在全身性脂多糖(LPS)或IL-1诱导的发热期间诱导。我们已经检查了腹腔注射IL-1激动剂IL-1α和IL-1β后的发热和细胞因子反应,并将其与对LPS(i. p.)在野生型和IL-1β缺陷小鼠中。IL-1β缺陷小鼠似乎体温升高,但表现出正常的昼夜温度周期。外源性注射IL-1β、IL-1α或LPS可诱导IL-1β缺陷小鼠的过敏性发热。我们还观察到野生型和IL-1β缺陷小鼠在下丘脑IL-1α和IL-6基础mRNA水平上的表型差异,但未观察到IL-1β转换酶或IL-1受体I型或II型的差异。与野生型小鼠相比,IL-1β缺陷小鼠下丘脑中IL-1α mRNA水平下调,而IL-6 mRNA水平上调。与野生型小鼠相比,IL-1β缺陷型小鼠对LPS攻击的反应也显著更高的血清皮质酮和更低的血清肿瘤坏死因子α水平。这些数据表明,在促炎细胞因子的冗余级联反应中,IL-1β在LPS或IL-1α诱导发热以及LPS或IL-1α或IL-1β诱导血清肿瘤坏死因子α型和皮质酮反应中起重要但非强制性作用。
IL-1β is an endogenous pyrogen that is induced during systemic lipopolysaccharide (LPS)- or IL-1-induced fever. We have examined the fever and cytokine responses following i.p. injection of IL-1 agonists, IL-1α and IL-1β, and compared these with response to LPS (i.p.) in wild-type and IL-1β-deficient mice. The IL-1β deficient mice appear to have elevated body temperature but exhibit a normal circadian temperature cycle. Exogenously injected IL-1β, IL-1α, or LPS induced hyperresponsive fevers in the IL-1β-deficient mice. We also observed phenotypic differences between wild-type and IL-1β-deficient mice in hypothalamic basal mRNA levels for IL-1α and IL-6, but not for IL-1β-converting enzyme or IL-1 receptor type I or type II. The IL-1α mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-1β-deficient mice as compared with wild-type mice. The IL-1β-deficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type α levels than the wild-type mice. The data suggest that, in the redundant cascade of proinflammatory cytokines, IL-1β plays an important but not obligatory role in fever induction by LPS or IL-1α, as well as in the induction of serum tumor necrosis factor type α and corticosterone responses either by LPS or by IL-1α or IL-1β.
DOI: 10.4049/jimmunol.157.1.291
发表时间: 1996-07
影响因子: 4.4
作者:
G. Fantuzzi;Hui Zheng;R. Faggioni;F. Benigni;P. Ghezzi;J. Sipe;A. Shaw;C. Dinarello
通讯作者: G. Fantuzzi;Hui Zheng;R. Faggioni;F. Benigni;P. Ghezzi;J. Sipe;A. Shaw;C. Dinarello