| | |  | | | | Record from Web of Science® | | | | | | |
| GRANULOCYTE COLONY-STIMULATING FACTOR TREATMENT PROTECTS RODENTS AGAINST LIPOPOLYSACCHARIDE-INDUCED TOXICITY VIA SUPPRESSION OF SYSTEMIC TUMOR-NECROSIS-FACTOR-ALPHA |
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| Author(s): GORGEN I, HARTUNG T, LEIST M, NIEHORSTER M, TIEGS G, UHLIG S, WEITZEL F, WENDEL A |
| Source: JOURNAL OF IMMUNOLOGY Volume: 149 Issue: 3 Pages: 918-924 Published: AUG 1 1992 |
| Times Cited: 189 References: 50 |
| Abstract: Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock. Intravenous injection of 250-mu-g/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50-mu-g/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis. In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice were pretreated with 50-mu-/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased. The suppressive effect bf G-CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats. However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected. These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages. To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation. The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CONSTANCE, FAC BIOL, POB 5560, W-7750 CONSTANCE, GERMANY |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: JF474 |
| ISSN: 0022-1767 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |