Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent

Camargo, Carlos A.; Madden, John F.; Gao, Wenshi; Selvan, Rathinam S.; Clavien, Pierre Alain

doi:10.1002/hep.510260619

Cited by 371 publications

(205 citation statements)

References 37 publications

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“…[21][22][23] Our hypothesis is that this process of hepatocyte proliferation could enhance HCV incorporation into the new hepatocyte within the allograft. Although no correlation was found in 1 study between the duration of cold preservation and severity of post-OLT HCV infection, 5 other types of injury related to organ preservation, such as the duration of graft rewarming during implantation surgery, could be important.…”

mentioning

confidence: 99%

Prolonged Rewarming Time During Allograft Implantation Predisposes to Recurrent Hepatitis C Infection After Liver Transplantation

Baron

Sindram

Higdon

et al. 2000

Liver Transplantation

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The majority of patients undergoing orthotopic liver transplantation (OLT) have end-stage liver disease secondary to hepatitis C virus (HCV) infection. Although OLT does not cure the disease and recurrent virus is present in all patients, relatively few patients with recurrent viremia develop clinical disease. When the disease recurs, however, the results can be devastating. Factors associated with increased risk for recurrent HCV disease remain controversial. We hypothesized that preservation injury may predispose to the severity of HCV disease after OLT. We reviewed our series of OLTs performed for HCV cirrhosis between January 1994 and December 1998 (n ‫؍‬ 56; 62 transplants). Patients were grouped according to the severity of recurrent hepatitis C. Group 1 had no or mild HCV disease (n ‫؍‬ 36), and group 2 had moderate to severe HCV disease (n ‫؍‬ 20). The duration of ischemic rewarming during graft implantation was significantly associated with the severity of recurrent hepatitis C (P F .04). The estimated chances of severe disease within the first year post-OLT after 30, 60, or 90 minutes of ischemic rewarming time were 19%, 40%, and 65%, respectively. Cold ischemia time, transaminase levels, and prothrombin time did not correlate with the severity of hepatitis C. In conclusion, our data suggest that the duration of ischemic rewarming predisposes to severe recurrent hepatitis C. This finding warrants the investigation of the pathogenesis of recurrent HCV disease after ischemic injury. Reduction of rewarming time should be stressed in OLT, particularly in patients with HCV cirrhosis. (Liver Transpl 2000;6:407-412.)A pproximately 1% of Americans (2.7 million individuals) are currently infected with the hepatitis C virus (HCV). 1 Although the natural history of the viral infection is unknown, it is estimated that chronic hepatitis caused by HCV infection develops in approximately 20% of infected individuals 20 years after initial exposure. 2-4 Patients with chronic HCV have an increased risk for hepatocellular carcinoma (1% to 4% per year) and the complications of end-stage liver disease. In these patients, the survival rate with decompensated cirrhosis is 50% at 5 years without transplantation. Orthotopic liver transplantation (OLT) for these patients leads to 5-year survival rates between 73% and 81%. 5,6 As a result of these data, patients with decompensated HCV cirrhosis should be considered for liver replacement therapy, as well as medical treatment, for better long-term survival. HCV-associated cirrhosis was the predominant indication for OLT in patients who underwent transplantation in the United States between 1987 and 1995. 7 Currently, hepatitis C is the indication for transplantation in more than 30% of adults, making it the most common indication for OLT. 8 Although several studies have suggested that the long-term survival rate after OLT in patients with HCV cirrhosis is not different from those who undergo OLT for other indications, 5,6,9,10 all patients have recurrent HCV infection at 1 year ...

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mentioning

confidence: 99%

Prolonged Rewarming Time During Allograft Implantation Predisposes to Recurrent Hepatitis C Infection After Liver Transplantation

Baron

Sindram

Higdon

et al. 2000

Liver Transplantation

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“…1,2 Various mechanisms have been proposed including enhanced production of inflammatory mediators, [3][4][5] recruitment of polymorphonuclear leukocytes (PMN), 6,7 and blockage of blood flow. [7][8][9] The leukocyte-endothelial interaction that occurs following ischemia/reperfusion (I/Rp) injury has been shown to be important for microvascular dysfunction and release of cytotoxic mediators such as reactive oxygen intermediates and a variety of proteases.…”

mentioning

confidence: 99%

P–Selectin Mediates Reperfusion Injury Through Neutrophil and Platelet Sequestration in the Warm Ischemic Mouse Liver

Yadav¹,

et al. 1999

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Hepatic damage following ischemia-reperfusion injury involves polymorphonuclear leukocytes (PMN) and platelet sequestration, however the mechanisms of adhesion remain elusive. In this study, using gene-targeted deficient mice, we evaluated P-selectin and its contribution to PMN and platelet adhesion in hepatic damage. In an in vivo warm ischemia model, hepatic injury was assessed by serum transaminase levels, survival, PMN adhesion by histological analysis, and platelet sequestration by immunostaining. Serum transaminase levels were strikingly reduced (by up to threefold) in the P-selectin deficient mice, particularly at 90 minutes of ischemia, when compared with wild-type controls. PMN adhesion and platelet sequestration was also significantly decreased in P-selectin deficient mice following 90 minutes of partial ischemia. Animal survival was significantly improved after 75 minutes of total hepatic ischemia in P-selectin deficient mice when compared with wild-type mice. Survival was also achieved after 90 minutes of ischemia in the mutant mice whereas none of the wild-type animals survived. These data show that P-selectin plays a critical role in PMN and platelet adhesion following ischemia-reperfusion injury to the liver. (HEPATOLOGY 1999; 29:1494-1502.)The pathogenesis of cell damage following reperfusion of ischemic tissue is an incompletely understood series of events. 1,2 Various mechanisms have been proposed including enhanced production of inflammatory mediators, 3-5 recruitment of polymorphonuclear leukocytes (PMN), 6,7 and blockage of blood flow. 7-9 The leukocyte-endothelial interaction that occurs following ischemia/reperfusion (I/Rp) injury has been shown to be important for microvascular dysfunction and release of cytotoxic mediators such as reactive oxygen intermediates and a variety of proteases. 10-12 We 13 and others 5,6,9,14,15 have shown leukocyte accumulation to be a critical determinant of hepatic I/Rp injury. Other blood elements including platelets adhere to the hepatic sinusoids in conditions of ischemia, 16,17 but little is known about their contribution to the injury.The adhesion of PMN and platelets to the vascular endothelium involves a variety of adhesion receptors. [18][19][20][21] The selectin family (P-, E-, and L-selectin) are the first to be engaged in the process, 19 with P-selectin acting at the earliest stage of interaction between PMN and the endothelium. P-selectin is found in the ␣ granules of resting platelets and Weibel-Palade bodies of endothelial cells, 18 and expression of P-selectin on the cell surface can occur within minutes under stimulation by mediators of inflammation such as thrombin, histamine, complement, and peroxide. 22 P-selectin is able to tether leukocytes to the endothelial surface through its ligand P-selectin glycoprotein ligand-1 (PSGL-1), which leads to their activation. 23 Once leukocytes attach, they can interact with flowing PMN and platelets through the action of P-and L-selectin, 23 which may lead to further adhesion of PMN and platelets as we...

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“…Van Andel, unpublished data). Given the role of IL-6 in neutrophil recruitment and TNF-AE modulation [12,14,17], isolate H1 might be expected to induce dramatically higher IL-6 levels than isolate M1. However, cytokine secretion is not always proportional to the inflammatory response.…”

Section: Grossmentioning

confidence: 99%

“…Specifically, IL-6 is important in neutrophil chemotaxis and activation [13] and is thought to modulate the immune response through downregulation of TNF-AE activity [14]. IL-6 is known to alter the severity and persistence of infections produced by several pathogens such as Listeria monocytogenes, Escherichia coli and Toxoplasma gondii [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Role of interleukin-6 in determining the course of murine Tyzzer's disease

Andel

Franklin

Besch‐Williford

et al. 2000

Journal of Medical Microbiology

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Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent

Cited by 371 publications

References 37 publications

Prolonged Rewarming Time During Allograft Implantation Predisposes to Recurrent Hepatitis C Infection After Liver Transplantation

Prolonged Rewarming Time During Allograft Implantation Predisposes to Recurrent Hepatitis C Infection After Liver Transplantation

P–Selectin Mediates Reperfusion Injury Through Neutrophil and Platelet Sequestration in the Warm Ischemic Mouse Liver

Role of interleukin-6 in determining the course of murine Tyzzer's disease

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