The in vivo contribution of hematopoietic cells to systemic TNF and IL-6 production during endotoxemia

被引:22
作者
Bultinck, Jennyfer
Brouckaert, Peter
Cauwels, Anje
机构
[1] Univ Ghent VIB, Mol Pathophysiol & Expt Therapy Unit, Dept Mol Biomed Res, B-9052 Ghent, Belgium
[2] Interuniv Inst Biotechnol, B-9052 Ghent, Belgium
关键词
TNF; IL-6; sepsis; bone marrow transplantation;
D O I
10.1016/j.cyto.2006.11.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:160 / 166
页数:7
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