Effect of endotoxin in IL-1 beta-deficient mice.
Effect of endotoxin in IL-1 beta-deficient mice.
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DOI：
10.4049/jimmunol.157.1.291
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发表时间：
1996-07
影响因子：
4.4
通讯作者：
G. Fantuzzi;Hui Zheng;R. Faggioni;F. Benigni;P. Ghezzi;J. Sipe;A. Shaw;C. Dinarello
中科院分区：
文献类型：
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作者：
G. Fantuzzi;Hui Zheng;R. Faggioni;F. Benigni;P. Ghezzi;J. Sipe;A. Shaw;C. Dinarello
IL-1在感染和炎症的病理生理反应中起重要作用，部分是通过介导其自身的产生和其他促炎细胞因子的产生。然而，IL-1 α和IL-1 β对炎症反应的相对贡献尚未得到很好的阐明。使用IL-1 β缺陷（IL-1 β-/-）小鼠，我们研究了IL-1 β在体内和体外对LPS的反应中的特定作用。在全身给予低剂量（5微克/千克）或高剂量（5毫克/千克）LPS后，IL-1 β +/+和IL-1 β-/-小鼠的IL-1 α、IL-6或TNF-α循环水平无差异。IL-1 β-/-小鼠在下丘脑-垂体-肾上腺轴激活、低血糖、血清淀粉样蛋白A产生和厌食方面对LPS也有正常反应。IL-1 β-/-小鼠通常对LPS的致死作用敏感，并且当用低剂量LPS预处理时可保护其免受LPS毒性。然而，在体外，来自用LPS刺激的IL-1 β-/-小鼠的腹膜巨噬细胞产生的IL-1 α显著少于来自IL-1 β +/+小鼠的巨噬细胞（p < 0.05）。在来自IL-1 β +/+和IL-1 β-/-小鼠的巨噬细胞之间未观察到IL-6或TNF-α合成的差异。总之，我们的研究结果表明，IL-1 β不是必需的体内全身反应LPS或其作用可以由其他细胞因子与重叠的活动。
IL-1 plays an important role in the pathophysiologic responses to infection and inflammation, in part by mediating its own production and that of other proinflammatory cytokines. However, the relative contribution of IL-1 alpha and IL-1 beta to the inflammatory response has not been well clarified. Using IL-1 beta-deficient (IL-1 beta -/-) mice, we investigated the specific role of IL-1 beta in the in vivo and in vitro response to LPS. No differences between IL-1 beta +/+ and IL-1 beta -/- mice were observed in circulating levels for IL-1 alpha, IL-6, or TNF-alpha after the systemic administration of either a low (5 micrograms/kg) or high (5 mg/kg) dose of LPS. IL-1 beta -/- mice also had a normal response to LPS in terms of activation of the hypothalamus-pituitary-adrenal axis, hypoglycemia, serum amyloid A production, and anorexia. IL-1 beta -/- mice were normally sensitive to the lethal effect of LPS and were protected against LPS toxicity when pretreated with low-dose LPS. However, in vitro, peritoneal macrophages from IL-1 beta -/- mice stimulated with LPS produced significantly less IL-1 alpha than macrophages from IL-1 beta +/+ mice (p < 0.05). No differences in IL-6 or TNF-alpha synthesis were observed between macrophages from IL-1 beta +/+ and IL-1 beta -/- mice. In summary, our results suggest that either IL-1 beta is not essential for the in vivo systemic response to LPS or that its role can be fulfilled by other cytokines with overlapping activities.