Granulocyte colony-stimulating factor prophylaxis improves survival and inflammation in a two-hit model of hemorrhage and sepsis*

Bauhofer, A.; Lorenz, W.; Kohlert, F.; Torossian, Alexander

doi:10.1097/01.ccm.0000201900.01000.6b

Cited by 14 publications

(11 citation statements)

References 40 publications

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“…Although the role of G-CSF in stimulating the production of neutrophils is well-established (2, 3) and G-CSF is used clinically to promote neutrophil production (4,5), it is clear that other cytokines contribute to the production and/or function of neutrophils. G-CSFdeficient mice (G Ϫ/Ϫ mice), or mice lacking the G-CSF receptor (G-CSFR Ϫ/Ϫ ), are viable but have markedly reduced numbers of circulating neutrophils (6 -8), establishing G-CSF as a major regulator of steady-state neutrophil production.…”

mentioning

confidence: 99%

Mice Lacking Three Myeloid Colony-Stimulating Factors (G-CSF, GM-CSF, and M-CSF) Still Produce Macrophages and Granulocytes and Mount an Inflammatory Response in a Sterile Model of Peritonitis

Hibbs¹,

Quilici²,

Kountouri³

et al. 2007

The Journal of Immunology

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To assess the combined role of G-CSF, GM-CSF, and M-CSF in myeloid cell production, mice deficient in all three myeloid CSFs were generated (G−/−GM−/−M−/− mice). G−/−GM−/−M−/− mice share characteristics found in mice lacking individual cytokines: they are toothless and osteopetrotic and furthermore acquire alveolar proteinosis that is more severe than that found in either GM−/− or G−/−GM−/− mice. G−/−GM−/−M−/− mice have a significantly reduced lifespan, which is prolonged by antibiotic administration, suggesting compromised ability to control bacterial infection. G−/−GM−/−M−/− mice have circulating neutrophils and monocytes, albeit at significantly reduced numbers compared with wild-type mice, but surprisingly, have more circulating monocytes than M−/− mice and more circulating neutrophils than G−/−GM−/− mice. Due to severe osteopetrosis, G−/−GM−/−M−/− mice show diminished numbers of myeloid cells, myeloid progenitors, and B lymphocytes in the bone marrow, but have significantly enhanced compensatory splenic hemopoiesis. Although G−/−GM−/−M−/− mice have a profound deficiency of myeloid cells in the resting peritoneal cavity, the animals mount a moderate cellular response in a model of sterile peritonitis. These data establish that in the absence of G-CSF, GM-CSF, and M-CSF, additional growth factor(s) can stimulate myelopoiesis and acute inflammatory responses.

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mentioning

confidence: 99%

Mice Lacking Three Myeloid Colony-Stimulating Factors (G-CSF, GM-CSF, and M-CSF) Still Produce Macrophages and Granulocytes and Mount an Inflammatory Response in a Sterile Model of Peritonitis

Hibbs¹,

Quilici²,

Kountouri³

et al. 2007

The Journal of Immunology

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“…However, it remains unclear how to reduce or prevent the subsequent severe sepsis after HS. Aggressive resuscitation, vasopressor therapy, nutritional support and antibiotic prophylaxis alone have been proven to be ineffective when trying to alter the cytokine expression and decrease the infection rate after HS (Esrig et al 1977; Chaudry and Ayala 1993; Bauhofer et al 2006). …”

Section: Future Studies: Hdaci In a Model Of Hemorrhagic And Subsequementioning

confidence: 99%

Creating a Pro-survival and Anti-inflammatory Phenotype by Modulation of Acetylation in Models of Hemorrhagic and Septic Shock

Alam

2011

Advances in Experimental Medicine and Biology

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Shock, regardless of etiology, is characterized by decreased tissue perfusion resulting in cell death, organ dysfunction, and poor survival. Current therapies largely focus on restoring tissue perfusion through resuscitation but have failed to address the specific cellular dysfunction caused by shock. Acetylation is rapidly emerging as a key mechanism that regulates the expression of numerous genes (epigenetic modulation through activation of nuclear histone proteins), as well as functions of multiple cytoplasmic proteins involved in key cellular functions such as cell survival, repair/healing, signaling, and proliferation. Cellular acetylation can be increased immediately through the administration of histone deacetylase inhibitors (HDACI). A series of studies have been performed using: (1) cultured cells; (2) single-organ ischemia-reperfusion injury models; (3) rodent models of lethal septic and hemorrhagic shock; (4) swine models of lethal hemorrhagic shock and multi-organ trauma; and (5) tissues from severely injured trauma patients, to fully characterize the changes in acetylation that occur following lethal insults and in response to treatment with HDACI. These data demonstrate that: (1) shock causes a decrease in acetylation of nuclear and cytoplasmic proteins; (2) hypoacetylation can be rapidly reversed through the administration of HDACI; (3) normalization of acetylation prevents cell death, decreases inflammation, attenuates activation of pro-apoptotic pathways, and augments pro-survival pathways; (4) the effect of HDACI significantly improves survival in lethal models of septic shock, hemorrhagic shock, and complex poly-trauma without need for conventional fluid resuscitation or blood transfusion; and (5) improvement in survival is not due to better resuscitation but due to an enhanced ability of cells to tolerate lethal insults. As different models of hemorrhagic or septic shock have specific strengths and limitations, this chapter will summarize our attempts to create “pro-survival and anti-inflammatory phenotype” in various models of hemorrhagic shock and septic shock.

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“…Si bien sûr le G-CSF peut être utilisé dans des cas de neutropénies, il semble aussi pouvoir présenter une valeur bénéfi que démontrée dans divers modèles infectieux [133]. Sans doute ses potentialités protectrices dépendent du type d'infection et du site d'infection [134].…”

Section: Granulocyte-colony Stimulating Factorunclassified

Médiateurs de l’inflammation au cours du sepsis

Cavaillon¹

2011

Sepsis Grave Et Choc Septique

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Au cours du sepsis, le processus infl ammatoire est initié suite à l'interaction des produits microbiens (pathogen associated molecular patterns [PAMPs]) avec les constituants de l'hôte, que ceux-ci soit des facteurs solubles (par exemple système du complément) ou des récepteurs membranaires (par exemple toll-like receptors) ou intracellulaires (par exemple nod-like receptors). Par ailleurs, des signaux endogènes générés par les dommages cellulaires et tissulaires (damage associated molecular patterns [DAMPs]) initiés par les agents microbiens vont également contribuer à l'initiation de la réponse infl ammatoire. La signalisation intracellulaire initiée par les PAMPs et les DAMPs aboutit à la production de nombreux média-teurs solubles de l'infl ammation. Parmi ceux-ci, les cytokines pro-infl ammatoires, et tout particulièrement l'interleukine-1 (IL-1) et le tumor necrosis factor (TNF), orchestrent une cascade de médiateurs qui contribuent directement au processus infl ammatoire. Parallèlement, des médiateurs anti-infl ammatoires tendant à limiter le processus infl ammatoire, sont également produits. Si le sepsis est associé dans les temps précoces à une production exacerbée de la majorité d'entre eux, on parle alors de tempête cytokinique, il faut garder en mémoire que la majorité de ces mêmes médiateurs de l'infl ammation sont essentiels à la mise en place de la réponse anti-infectieuse. Rappelons que la tempête cytokinique peut parfaitement être initiée en l'absence de signaux microbiens [1].

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Granulocyte colony-stimulating factor prophylaxis improves survival and inflammation in a two-hit model of hemorrhage and sepsis*

Abstract: Hemorrhage (first hit) sensitized the host for a second hit of polymicrobial PCI independent of the timing. G-CSF prophylaxis improved survival and clearance of microbes and reduced the proinflammatory chemokine macrophage inflammatory protein-2 in the lung.

Cited by 14 publications

References 40 publications

Mice Lacking Three Myeloid Colony-Stimulating Factors (G-CSF, GM-CSF, and M-CSF) Still Produce Macrophages and Granulocytes and Mount an Inflammatory Response in a Sterile Model of Peritonitis

Mice Lacking Three Myeloid Colony-Stimulating Factors (G-CSF, GM-CSF, and M-CSF) Still Produce Macrophages and Granulocytes and Mount an Inflammatory Response in a Sterile Model of Peritonitis

Creating a Pro-survival and Anti-inflammatory Phenotype by Modulation of Acetylation in Models of Hemorrhagic and Septic Shock

Médiateurs de l’inflammation au cours du sepsis

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