G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils

Spuck, S; Schaaf, Bernhard; Wiedorn, Klaus-Hermann; Hansen, F; Vollmer, Ekkehard; Dalhoff, K; Braun, J.

doi:10.1053/rmed.2002.1414

Cited by 12 publications

(10 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, NAC suppressed IL-10 secretion to a much greater degree than EP. Although our data were insufficient to provide a mechanism for the discordance between the pharmacological effects of EP and NAC on IL-10 mRNA expression and IL-10 secretion, discordance between changes in IL-10 transcript levels and changes in IL-10 secretion has been noted before (Ledeboer et al, 2002;Spuck et al, 2003). In this context, it is important to recognize that our measurements of IL-10 concentration in samples of conditioned media assessed the cumulative secretion of the cytokine over a 24-h period of incubation, whereas our semiquantitative estimates of IL-10 transcript levels represented a "snapshot" at a single point in time (i.e., 4 h after stimulation of cells with LPS).…”

Section: Discussionmentioning

confidence: 72%

Evidence That Glutathione Depletion Is a Mechanism Responsible for the Anti-Inflammatory Effects of Ethyl Pyruvate in Cultured Lipopolysaccharide-Stimulated RAW 264.7 Cells

Song

Kellum²,

Kaldas³

et al. 2003

J Pharmacol Exp Ther

116

View full text Add to dashboard Cite

Ethyl pyruvate (EP), an effective scavenger of reactive oxygen species, is also an anti-inflammatory agent in a variety of in vivo and in vitro model systems. To gain a better understanding of the molecular basis for the anti-inflammatory effects of EP, we compared the pharmacological properties of EP and N-acetyl-L-cysteine (NAC), a well studied scavenger of reactive oxygen species and a precursor for the endogenous antioxidant glutathione (GSH). The studies were performed using RAW 264.7 murine macrophage-like cells that were stimulated with lipopolysaccharide (LPS). Although EP and NAC both inhibited LPS-induced nitric oxide and interleukin (IL)-6 secretion, the former compound was considerably more potent than the latter. EP markedly inhibited inducible nitric-oxide synthase, IL-6, and IL-10 mRNA induction, whereas the effects of NAC were minimal. EP inhibited LPS-induced nuclear factor-B DNA binding to a much greater extent than did NAC. Both compounds inhibited LPS-induced lipid peroxidation, but the two compounds had qualitatively different effects on cellular levels of GSH. Although NAC increased GSH levels, EP had the opposite effect. The anti-inflammatory effects of EP were partially reversed when RAW 264.7 cells were treated with a cellpermeable GSH analog, glutathione ethyl ester. These data support the view that the anti-inflammatory effects of EP are mediated, at least in part, by the ability of EP to deplete cellular GSH stores. Moreover, the findings presented here suggest that an unusual combination of biochemical effects (inhibition of lipid peroxidation and GSH depletion) might account for the anti-inflammatory effects of EP.

show abstract

Section: Discussionmentioning

confidence: 72%

Evidence That Glutathione Depletion Is a Mechanism Responsible for the Anti-Inflammatory Effects of Ethyl Pyruvate in Cultured Lipopolysaccharide-Stimulated RAW 264.7 Cells

Song

Kellum²,

Kaldas³

et al. 2003

J Pharmacol Exp Ther

116

View full text Add to dashboard Cite

show abstract

“…(19) However, upregulation of such anti-inflammatory factors as sTNFRI, sTNFRII, and IL-1RA by G-CSF (20,21) may be the main anti-inflammatory effect and more important than the influence of G-CSF on IL-10 or TNF-a. (20) From in vitro studies of the expression of anti-inflammatory cytokines in leukocytes by G-CSF (22,23) and studies with G-CSF treatment in healthy subjects (20,21) and patients, (19,24) it is supposed that G-CSF plays a role in the upregulation of anti-inflammatory mediators despite its potential to aggravate lung injury. (8)(9)(10)25) Results of the present study demonstrate that in the early phase of disease, concentrations of G-CSF, TNF-a, and IL-6 in BALF and serum are higher in ARDS than in ALI.…”

Section: Discussionmentioning

confidence: 99%

Association of Endogenous G-CSF with Anti-Inflammatory Mediators in Patients with Acute Respiratory Distress Syndrome

Wiedermann

Mayr²,

Hobisch-Hagen³

et al. 2003

Journal of Interferon & Cytokine Research

View full text Add to dashboard Cite

Upregulation of the anti-inflammatory mediators, soluble tumor necrosis factor-alpha receptors I and II (sTNFRI/RII) and interleukin-1 receptor antagonist (IL-1RA), by granulocyte colony-stimulating factor (G-CSF) may contribute to the pathophysiology of lung injury. We determined the relation of endogenous G-CSF to proinflammatory and anti-inflammatory mediators in bronchoalveolar lavage fluid (BALF) and serum of patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Nineteen patients with ARDS and 10 with ALI were included in this prospective investigation. BAL was performed within 12 h and 24 h after onset of lung injury. Concentrations of G-CSF, TNF-alpha, IL-6, sTNFRI and sTNFRII, IL-1RA and IL-10 in BALF as well as in serum were determined by ELISA. G-CSF was associated with alveolar neutrophilia. Results in patients with ARDS and ALI exhibited significant positive correlations in BALF of G-CSF levels with that of IL-6, sTNFRII, and IL-1RA and of G-CSF levels in serum with that of serum IL-6, IL-1RA, and IL-10. Given the potential of G-CSF to directly induce anti-inflammatory cytokines in vitro, significant associations of endogenous G-CSF levels with these mediators early in the development of severe lung injury suggest an endogenous anti-inflammatory role of G-CSF in vivo.

show abstract

“…Demographic data, TNF-α and IL-10 protein and mRNA data were published earlier in a subanalysis [14]. The diagnosis of pneumonia was based on clinical symptoms and laboratory signs of infection (such as fever >38°C, purulent sputum, elevated ESR, C-reactive protein) together with the presence of new or progressing opacities on a chest radiograph.…”

Section: Methodsmentioning

confidence: 99%

Neutrophil Apoptosis, Activation and Anti-Inflammatory Cytokine Response in Granulocyte Colony-Stimulating Factor-Treated Patients with Community-Acquired Pneumonia

Droemann

Hansen²,

Aries³

et al. 2006

Respiration

View full text Add to dashboard Cite

Background:Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus. Objectives: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP. Methods: Patients received a single dose of G-CSF (1 × 300 or 480 µg s.c.) prior to standard antibiotic treatment (n = 8) or standard treatment only (n = 8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessedusing fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA. Results: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6 ± 9.7 vs. 71.2 ± 17.7, p < 0.01), neutrophil apoptosis decreased (apoptosis: 1.36 ± 0.27 vs. 0.2 ± 0.12%, p < 0.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4 ± 72.2 vs. 340.1 ± 194.6 ng/ml, p < 0.01; sTNF-p55 382 ± 4,243 vs. 632 ± 4,714 ng/ml, p < 0.01; control group nonsignificant). These effects were not seen in the control group. Conclusions: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.

show abstract

G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils

Cited by 12 publications

References 27 publications

Evidence That Glutathione Depletion Is a Mechanism Responsible for the Anti-Inflammatory Effects of Ethyl Pyruvate in Cultured Lipopolysaccharide-Stimulated RAW 264.7 Cells

Evidence That Glutathione Depletion Is a Mechanism Responsible for the Anti-Inflammatory Effects of Ethyl Pyruvate in Cultured Lipopolysaccharide-Stimulated RAW 264.7 Cells

Association of Endogenous G-CSF with Anti-Inflammatory Mediators in Patients with Acute Respiratory Distress Syndrome

Neutrophil Apoptosis, Activation and Anti-Inflammatory Cytokine Response in Granulocyte Colony-Stimulating Factor-Treated Patients with Community-Acquired Pneumonia

Contact Info

Product

Resources

About