Treatment with recombinant bactericidal/permeability-increasing protein to prevent endotoxin-induced mortality in bile duct-ligated rats

Kimmings, A. N.; Deventer, S. J. H. Van; Obertop, H.; Gouma, Dirk J.

doi:10.1016/s1072-7515(99)00164-7

Cited by 26 publications

(13 citation statements)

References 20 publications

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“…One hypothesis is that cholestasis leads to translocation of bacteria and endotoxin across gut mucosa, a phenomenon readily observed in animal models of cholestasis. [23][24][25][26] The presence of Flu in the conditioning regimen was marginally associated with an increased risk of developing jaundice after HCT. Phase 1 studies of Flu outside of the transplantation setting generally do not report hepatotoxicity as a serious problem.…”

Section: Discussionmentioning

confidence: 99%

Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients

Hogan

Maris

Storer

et al. 2004

Blood

150

105

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Liver injury is a frequent, serious complication of allogeneic hematopoietic cell transplantation (HCT) following myeloablative preparative regimens. We sought to determine the frequency and severity of hepatic injury after nonmyeloablative conditioning and its relationship to outcomes. One hundred ninety-three consecutive patients who received 2 Gy total body irradiation with or without fludarabine were evaluated for end points related to liver injury. Patients with diseases treatable by HCT who were ineligible for conventional myeloablative allogeneic HCT because of advanced age and/or comorbid conditions were included. Fifty-one patients (26%) developed hyperbilirubinemia of 68.4 M (4 mg/dL) or greater, most commonly resulting from cholestasis due to graft-versushost disease (GVHD) or sepsis. Pretransplantation factors associated with liver dysfunction were a diagnosis of aggressive malignancy (hazard ratio [HR] 1.9; P ‫؍‬ .04) and the inclusion of fludarabine in the conditioning regimen (HR 1.8; P ‫؍‬ .07). Overall survival at 1 year was superior for patients who had maximal serum bilirubin levels in the normal (78%) or minimally elevated (

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Section: Discussionmentioning

confidence: 99%

Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients

Hogan

Maris

Storer

et al. 2004

Blood

150

105

View full text Add to dashboard Cite

show abstract

“…Inactivation of endotoxin with bactericidalpermeability-increasing protein (35) or with polymyxin B (36) improved mortality and morbidity in bile duct-ligated rats. Hence, from animal models of obstructive jaundice, a causative role of endotoxin in postoperative complications can be concluded.…”

mentioning

confidence: 99%

Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production

Parlesak

Schaeckeler

Moser

et al. 2007

Critical Care Medicine

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“…9 In addition, cholestasis is associated with enhanced susceptibility toward endotoxin-induced toxicity. [9][10][11][12][13][14] Endotoxin exerts its biological effects by activating immunocompetent cells such as monocytes and macrophages. After exposure to endotoxin, these cells readily release various inflammatory mediators such as the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), 15 which leads to an inflammatory response.…”

mentioning

confidence: 99%

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

et al. 2002

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Cholestatic liver injury is associated with an increased susceptibility toward endotoxininduced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R ؊/؊ ) mice, which are unresponsive to IL-1␣ and IL-1␤, and normal IL-1R ؉/؉ mice. Bdl elicited increases in hepatic IL-1␣ and IL-1␤ messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R ؊/؊ and IL-1R ؉/؉ mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in shamoperated IL-1R ؊/؊ and IL-1R ؉/؉ mice were largely similar, but cholestatic IL-1R ؊/؊ mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1␣ and IL-1␤ are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl. S urgery in jaundiced patients with periampullary tumors carries an increased risk of postoperative complications. 1 Whereas in experienced centers, postoperative mortality has been reduced from 20% to 5%, morbidity remains as high as 50%. 2,3 Most complications have a septic etiology and are considered to be related with translocation of endotoxin from the intestinal lumen into the portal and systemic circulation where an inflammatory cascade is triggered. 4,5 Potential causes of translocation of endotoxin include lack of bile salts in the intestinal lumen resulting in increased bacterial translocation, 6,7 decreased function of the resident macrophages of the liver (the Kupffer cells) leading to inadequate interception of endotoxin, 6-8 and changes in plasma concentrations of lipoproteins which bind endotoxin. 9 In addition, cholestasis is associated with enhanced susceptibility toward endotoxin-induced toxicity. [9][10][11][12][13][14] Endotoxin exerts its biological effects by activating immunocompetent cells such as monocytes and macrophages. After exposure to endotoxin, these cells readily release various inflammatory mediators such as the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), 15 which leads to an inflammatory response. The Kupffer cells are also capable of releasing these cytokines in response to endotoxin. 16,17 IL-1␣ and IL-1␤ are pleiotropic proinflammatory cytokines that are considered to play a proximal role in initiation and regulation of the inflammatory cascade triggered in response to endotoxins or bacteremia. 15,18 Both IL-1␣ and IL-1␤ can interact with two specific cell surface receptors, the type I and type II IL-1 receptor (IL-1R), of ...

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Treatment with recombinant bactericidal/permeability-increasing protein to prevent endotoxin-induced mortality in bile duct-ligated rats

Cited by 26 publications

References 20 publications

Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients

Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients

Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

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