Granulocyte Colony-Stimulating Factor Enhances Killing of Translocated Bacteria but does not Affect Barrier Function in a Burn Mouse Model

Eaves-Pyles, Tonyia; Alexander, J. Wesley

doi:10.1097/00005373-199612000-00012

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…Therefore, we suggest that the ability of immunonutrition to prevent BT is probably related to improvement of host immunity. Our finding supports many other studies which have shown that BT was prevented without improvement in intestinal mucosal barrier [38][39][40]. In a rat model of burn wound sepsis, Yalcin et al [38] reported that both the control and granulocyte colony-stimulating factor (g-csf) treated rats had disrupted mucosal barrier manifested with blunted villae in distal ileum.…”

Section: Discussionsupporting

confidence: 90%

“…We support the finding of this study which presented that disrupted mucosal integrity led to BT, but improvement in mucosal barrier is not a prerequisite for prevention of BT. In another study, Eaves-Pyles and Alexander [39] investigated the effect of g-csf on bacterial translocation in a gut-derived sepsis after burn injury and suggested that treatment with g-csf did not improve gut barrier function, but did enhance the host's ability to kill translocated organisms and improved survival. Unal et al [40] has also reported that activation of inflammatory response with granulocyte macrophage colony-stimulating factor (gm-csf) prevented BT caused by obstructive jaundice without improving the injured gut mucosa.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Different Enteral Nutrients on Bacterial Translocation in Experimental Obstructive Jaundice

Kuru¹,

Dinç²,

Altınok

et al. 2004

Eur Surg Res

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Obstructive jaundice leads to bacterial translocation (BT) by disruption of the gut barrier, intestinal microecology, and impaired host immune defence. The objective of the present study is to investigate the effects of different enteral nutrients on BT that is induced by obstructive jaundice in rats. Eighty male Wistar-Albino rats were randomly assigned into 4 groups. Group 1: 20 rats underwent laparotomy, common bile duct (CBD) was not actually ligated and transected, but sham ligation of CBD was performed. Groups 2–4: 60 rats underwent laparotomy, CBD ligation and transection. Group 1 and 2 rats were given rat chow, group 3 rats were fed a glutamine and arginine supplemented enteral diet, and group 4 rats were fed an arginine, m-RNA and ω-3 supplemented enteral diet, an immunonutrient. Rats in groups 3 and 4 had significantly less BT to mesenteric lymph nodes compared to rats in group 2 (p = 0.001). These findings suggest that oral administration of an arginine and glutamine supplemented diet and immunonutrition reduce BT in rats with obstructive jaundice.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Effect of Different Enteral Nutrients on Bacterial Translocation in Experimental Obstructive Jaundice

Kuru¹,

Dinç²,

Altınok

et al. 2004

Eur Surg Res

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“…The most evident effect of G-CSF pretreatment is the significant increase in both the number of peripheral neutrophils and their phagocytic activity. This increase presumably leads to improved control of the infection in the systemic compartment by reducing the number of bacteria (1,4,6,12,13,19,21,22,24,26), as also seen in the present study. In pneumococcal meningitis, approximately 70% of patients become bacteremic, and bacteremia has been associated with an increased risk of mortality (5, 10, 11, 25; D. van de Beek and J. de Gans, Abstr.…”

Section: Discussionsupporting

confidence: 80%

Attenuation of the Bacterial Load in Blood by Pretreatment with Granulocyte-Colony-Stimulating Factor Protects Rats from Fatal Outcome and Brain Damage duringStreptococcus pneumoniaeMeningitis

Brandt

Lundgren²,

Lund

et al. 2004

Infect Immun

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A model of pneumococcal meningitis in young adult rats receiving antibiotics once the infection was established was developed. The intent was to mimic clinical and histopathological features of pneumococcal meningitis in humans. The primary aim of the present study was to evaluate whether medical boosting of the peripheral neutrophil count affected the outcome of the meningitis. The risk of terminal illness over the first 7 days after infection was significantly reduced for rats who had elevated peripheral white blood cell counts after receiving granulocyte-colony-stimulating factor (G-CSF) prior to the infection compared to that for untreated rats (P ‫؍‬ 0.039 by the log rank test). The improved outcome was associated with reduced signs of cerebral cortical damage (P ‫؍‬ 0.008). Furthermore, the beneficial effects of G-CSF were associated with reduced bacterial loads in the cerebrospinal fluid (median, 1.1 ؋ 10 5 versus 2.9 ؋ 10 5 CFU/ml; P ‫؍‬ 0.023) and in blood (median, 2.9 ؋ 10 2 versus 6.3 ؋ 10 2 CFU/ml; P ‫؍‬ 0.024), as well as attenuated pleocytosis (median, 800 ؋ 10 6 versus 1,231 ؋ 10 6 cells/liter; P ‫؍‬ 0.025), 24 h after the infection. Conversely, initiation of G-CSF therapy 28 h postinfection did not alter the clinical or histological outcome relative to that for non-G-CSFtreated rats. The magnitude of bacteremia and pretreatment with G-CSF were found to be prognostic factors for both outcome and brain damage. In summary, elevated neutrophil levels prior to the development of meningitis result in reduced risks of death and brain damage. This beneficial effect is most likely achieved through improved control of the systemic disease.

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“…Following arrival in the MLN these molecules then disseminate systemically [1–3]. Enteric bacteria and their products, including bacterial lipopolysaccharide (LPS), have been implicated in the development of sepsis and multiple organ dysfunction syndrome (MODS) increasing morbidity and mortality in burn patients [4].…”

Section: Introductionmentioning

confidence: 99%

Intraluminal Flagellin Differentially Contributes to Gut Dysbiosis and Systemic Inflammation following Burn Injury

et al. 2016

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Burn injury is associated with a loss of gut barrier function, resulting in systemic dissemination of gut-derived bacteria and their products. The bacterial protein and TLR5 agonist, flagellin, induces non-specific innate immune responses. Because we detected flagellin in the serum of burn patients, we investigated whether gut-derived flagellin was a primary or secondary contributor to intestinal dysfunction and systemic inflammation following burn injury. The apical surface of polarized human intestinal epithelial cells (IECs), Caco-2BBe, were exposed to 50 or 500 ng of purified flagellin and 1 x 105 of an intestinal E. coli (EC) isolate as follows: 1) flagellin added 30 min prior to EC, 2) flagellin and EC added simultaneously, or 3) EC added 30 min prior to flagellin. Our results showed that luminal flagellin and EC modulated each other's biological actions, which influenced their ability to induce basolateral secretion of inflammatory cytokines and subsequent translocation of bacteria and their products. A low dose of flagellin accompanied by an enteric EC in the lumen, tempered inflammation in a dose- and time-dependent manner. However, higher doses of flagellin acted synergistically with EC to induce both intestinal and systemic inflammation that compromised barrier integrity, increasing systemic inflammation following burn injury, a process we have termed flagellemia. In a murine model of burn injury we found that oral gavage of flagellin (1 μg/mouse) significantly affected the gut microbiome after burn injury. In these mice, flagellin disseminated out of the intestine into the serum and to distal organs (mesenteric lymph nodes and lungs) where it induced secretion of monocyte chemoattractant protein (MCP-1) and CXCL1/KC (mouse equivalent of human IL-8) at 24 and 48h post-burn. Our results illustrated that gut-derived flagellin alone or accompanied by a non-pathogenic enteric EC strain can function as an initiator of luminal and systemic inflammation following burn injury.

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Granulocyte Colony-Stimulating Factor Enhances Killing of Translocated Bacteria but does not Affect Barrier Function in a Burn Mouse Model

Abstract: These data suggest that treatment with mG-CSF does not improve gut barrier function, but does enhance the host's ability to kill translocated organisms and improve survival in a gut-derived sepsis model.

Cited by 15 publications

References 22 publications

Effect of Different Enteral Nutrients on Bacterial Translocation in Experimental Obstructive Jaundice

Effect of Different Enteral Nutrients on Bacterial Translocation in Experimental Obstructive Jaundice

Attenuation of the Bacterial Load in Blood by Pretreatment with Granulocyte-Colony-Stimulating Factor Protects Rats from Fatal Outcome and Brain Damage duringStreptococcus pneumoniaeMeningitis

Intraluminal Flagellin Differentially Contributes to Gut Dysbiosis and Systemic Inflammation following Burn Injury

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