The in vivo contribution of hematopoietic cells to systemic TNF and IL-6 production during endotoxemia
The in vivo contribution of hematopoietic cells to systemic TNF and IL-6 production during endotoxemia
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DOI：
10.1016/j.cyto.2006.11.010
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发表时间：
2006-11-01
期刊：
影响因子：
3.8
通讯作者：
Cauwels, Anje
中科院分区：
文献类型：
--
作者：
Bultinck, Jennyfer;Brouckaert, Peter;Cauwels, Anje
脓毒症是由于对感染的不适当的先天免疫反应而引起的全身炎症反应综合征。TNF和白细胞介素（IL）-6在该综合征中起关键作用，尽管缺乏确凿的体内证据，但先天性免疫细胞被认为是这些细胞因子的主要生产者。我们通过在LPS敏感（C3 H/HeN）和LPS低反应（C3 H/HeJ）小鼠之间进行骨髓移植（BMT）来研究这一假设。对于足够的LPS诱导的全身TNF的生产，造血细胞群体是绝对必要的。与此相反，IL-6可以检测到在循环中的LPS处理的嵌合体小鼠，其中无论是造血或实质细胞群体是低反应的LPS。因此，尽管在LPS诱导的脓毒症模型中造血细胞是全身性TNF的唯一来源，但造血细胞和实质细胞都是全身性IL-6产生所需的。此外，LPS诱导的实质细胞中IL-6的产生可能部分由TNF/TNF-R1途径介导，如LPS处理的野生型（WT）、TNF-R1缺陷和嵌合小鼠中的全身IL-6水平所证明的。(c)2006爱思唯尔有限公司保留所有权利。
Sepsis is a systemic inflammatory response syndrome resulting from an inappropriate innate immune response to infection. TNF and interleukin (IL)-6 are critically involved in this syndrome and although conclusive in vivo evidence is missing, innate immune cells are believed to be the principal producers of these cytokines. We investigated this assumption by performing bone marrow transplantations (BMT) between LPS-sensitive (C3H/HeN) and LPS-hyporesponsive (C3H/HeJ) mice. For adequate LPS-induced systemic TNF production, the hematopoietic cell population was absolutely required. In contrast, IL-6 could be detected in the circulation of LPS-treated chimeric mice, of which either the hematopoietic or the parenchymal cell population was hyporesponsive to LPS. So, whereas hematopoietic cells are the sole source of systemic TNF in an LPS-induced model of sepsis, both hematopoietic and parenchymal cells are required for systemic IL-6 production. Moreover, LPS-induced IL-6 production in parenchymal cells may be partially mediated by the TNF/TNF-R1 pathway as evidenced by the systemic IL-6 levels in LPS-treated wild type (WT), TNF-R1-deficient and chimeric mice. (c) 2006 Elsevier Ltd. All rights reserved.