| Автор | Hartung, T. |
| Автор | Volk, H-D. |
| Автор | Wendel, A. |
| Дата выпуска | 1995 |
| dc.description | We have previously reported that in various macrophage populations prepared from G-CSF treated rats LPS-inducible TNF release was suppressed. In vitro, LPS induced liver cell death only when hepatocytes were cocultured with liver macrophages. Rat Kupffer cells from G-CSF treated donor animals were less potent in mediating LPS-inducible hepatocytotoxicity in vitro than cells from control animals. These ex vivo findings were confirmed in vivo by demonstrating that G-CSF treatment attenuated LPS-inducible circulating TNF levels and protected from liver injury and mortality.We extended these observations to humans in two studies with G-CSF treated volunteers. In a pilot study, 11 subjects were treated single-blindly with 480 μg G-CSF s.c. (n = 7) or saline placebo (n = 4). Blood was taken at different time-points relative to G-CSF injection and cytokine release capacity was assessed in LPS stimulated whole blood incubations. In blood from G-CSF treated volunteers, we found reduced LPS-inducible TNF formation while the release of both soluble TNF receptor (sTNF-R) and interleukin 1 receptor antagonist (IL-1ra) were increased. In a second double-blind, randomized and controlled study, three groups of seven volunteers were treated once or twice 24 h apart with G-CSF or solvent placebo. Besides LPS, various stimuli were included to initiate cytokine release in a whole blood assay. The reduction of TNF formation (mean 53 % at 24 h after G-CSF) was different with the various stimuli. All stimuli increased IL-1ra (mean 14-fold) and sTNF-R (mean 3-fold) at 24 h after G-CSF. LPS-inducible IFN-γ and GM-CSF were significantly reduced. Our data indicate that the pattern of cytokines produced by human whole blood taken after G-CSF treatment in response to a variety of stimuli is shifted from pro- to anti-inflammatory mediators. These findings extend the knowledge on the pharmacology of G-CSF in animal models of the systemic inflammatory response syndrome and prompt a trial of G-CSF prophylaxis with this indication. |
| Издатель | Sage Publications |
| Название | G-CSF - an anti-inflammatory cytokine |
| Тип | Journal Article |
| DOI | 10.1177/096805199500200308 |
| Print ISSN | 0968-0519 |
| Журнал | Journal of Endotoxin Research |
| Том | 2 |
| Первая страница | 195 |
| Последняя страница | 201 |
| Аффилиация | Hartung, T., Department of Biochemical Pharmacology, University of Konstanz, Department of Clinical Immunology, Charité Berlin, Germany |
| Аффилиация | Volk, H-D., Department of Biochemical Pharmacology, University of Konstanz, Department of Clinical Immunology, Charité Berlin, Germany |
| Аффилиация | Wendel, A., Department of Biochemical Pharmacology, University of Konstanz, Department of Clinical Immunology, Charité Berlin, Germany |
| Выпуск | 3 |
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