The in vivo contribution of hematopoietic cells to systemic TNF and IL-6 production during endotoxemia.
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.
Bultinck
Jennyfer
J
Molecular Pathophysiology and Experimental Therapy Unit, Department of Molecular Biomedical Research, Ghent University and Flanders Interuniversity Institute of Biotechnology (VIB), Ghent (Zwijnaarde), Belgium. Jennyfer.Bultinck@isrec.ch
Brouckaert
Peter
P
Cauwels
Anje
A
D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D019446:Endotoxemia / Q000097:blood*; D005260:Female; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014916:Whole-Body Irradiation
D015850:Interleukin-6; D008070:Lipopolysaccharides; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha