Involvement of tumor necrosis factor-α in the pathogenesis of activated macrophage-mediated hepatitis in mice

Nagakawa, Junichi; Hishinuma, Ieharu; Hirota, Kazuo; Miyamoto, Ko Ichiro; Yamanaka, Takashi; Tsukidate, Kazuo; Katayama, Kouichi; Yamatsu, Isao

doi:10.1016/0016-5085(90)90965-4

Cited by 125 publications

(85 citation statements)

References 26 publications

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“…For this purpose, a careful evaluation of the patient's medical condition using objective physiological data seems a useful method to select the candidates. Taking into account the organ shortage, our results suggest that an ELT should not be performed in patients with a massive liver necrosis and cardiac failure, an APACHE I1 score greater than 30 or more than 2 OSF. New therapeutic approaches are mandatory for patients with liver failure complicated by MOF. Ringe et a1 have stressed that the shorter the time with a definitely necrotized liver, the better the survival rate would be."…”

Section: Discussionmentioning

confidence: 89%

How valid is emergency liver transplantation for acute liver necrosis in patients with multiple-organ failure?

et al. 1996

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Multiple‐organ failure (MOF), defined as the failure of initially uninvolved organs, is the final step of definitive and massive liver necrosis. Emergency liver transplantation (ELT) has radically modified the outcome of acute liver failure and early primary graft failure, but the results of ELT in cases of MOF are unknown. From May 1988 to June 1993, 243 patients underwent a liver transplantation (LT). Thirty‐seven patients (15.2%) who had an acute liver necrosis complicated by a MOF underwent an ELT. Twenty‐one patients were children. An emergency retransplantation was performed in 16 patients. Three or 4 organ‐system failures (OSF) were present in 13 patients. Before ELT, the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 26.3 ± 5.1. Six‐month and 1‐year survival rates were 37.8% and 25.9%, respectively, after ELT complicated by MOF, and 78% and 73.5%, respectively, in other cases of LT. Twenty‐six patients had surgical complications (70%), whereas thirty‐one patients had medical complications (84%). Twentytwo patients died during the postoperative period (60%). Before ELT, infection (P < .05), cardiovascular failure (P < .03), and more than two OSF (P < .05) were more frequent in patients who died after intervention. The APACHE II score (P < .05) and the length of stay in the intensive care unit before ELT (P < .05) were lower among survivors. In the context of liver allograft shortage, our results suggest that an ELT should not be performed in patients with cardiac failure, more than two OSF, or an APACHE II score higher than 30. Copyright © 1996 by the American Association for the Study of Liver Diseases.

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Section: Discussionmentioning

confidence: 89%

How valid is emergency liver transplantation for acute liver necrosis in patients with multiple-organ failure?

et al. 1996

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“…This latter hypothesis is unlikely, however. as the utilization of monoclonal antibodies to IL-6 does not impair regeneration but does reduce tissue injury following a variety of tissue insults (15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the liver has a unique capacity for TNF production. Previous studies using diverse models of hepatotoxicity have suggested that TNF,js a terminal mediator of liver injury (15)(16)(17). Indeed.…”

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confidence: 99%

“…Indeed. TNF has been suggested to play a role in models such as galactosamine liver injury (15), lead-enhanced endotoxic liver injury (16) and antibodies have been shown to block or attenuate these models of liver injury (15,17). TNF is known to be involved in many inflammatory processes, and it can be detected during renal (18) and cardiac (19) allograft rejection.…”

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confidence: 99%

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FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion

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McClain

Gavaler

et al. 1993

Journal of Hepatology

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HEPAT 01243FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemiajreperfusion Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (OJ mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats that were given FK 506 6 and 24 h prior to the induction of the hepatic ischemic insult (70% and 80% 10-day survival rates, respectively). The hepatoprotective effect of FK 506 was assessed further in a second experiment in which the serum levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) were measured. These results suggest that a 60-min period of hepatic ischemia and subsequent reperfusion triggers the release of both TNF and IL-6, and that FK 506 pre-treatment (6 h before the ischemic episode) significantly inhibits the production and/or release of these two cytokines compared to untreated controls. These data provide additional information concerning the immunosuppressive and hepatoprotective activities of FK 506. Based upon these data, it is probable that FK 506 attenuates hepatic ischemiajreperfusion injury, at least in part, by reducing TNF and IL-6 levels.

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“…7 In the P. acnes model, activated hepatic macrophages after endotoxin stimulation destroyed sinusoidal endothelial cells by releasing superoxide anions and tumor necrosis factor ␣ and provoked fibrin deposition in the hepatic sinusoids. 2,5,6,[8][9][10] Such mechanisms, however, may not be involved in the development of sinusoidal fibrin deposition in the partialhepatectomy model, because polyclonal antibody against tumor necrosis factor ␣ and superoxide anion dismutase were ineffective for attenuation of the liver injury. 3,6 Moreover, selective eradication of large hepatic macrophages responsible for production of cytotoxic mediators using gadolinium chloride 11 significantly attenuated liver injury in the P. acnes model, but not liver injury in the partial-hepatectomy model, 5,6 whereas suppression of activation of Kupffer cells and hepatic macrophages by pretreatment of gum arabic 12 produced similar attenuation of liver injuries in both models.…”

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confidence: 99%

Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats

et al. 1999

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Activated Kupffer cells provoke massive liver necrosis after endotoxin stimulation through microcirculatory disturbance caused by sinusoidal fibrin deposition in rats undergoing 70% hepatectomy. In these rats, serum activities of purine nucleoside phosphorylase (PNP) and alanine transaminase (ALT) were increased at 1 and 5 hours, respectively, following endotoxin administration. When 70% resected liver was perfused with Dulbecco's modified Eagle medium (DMEM) containing heat-inactivated fetal calf serum, the increase in both enzyme activities was not affected by addition of endotoxin during perfusion, suggesting that activated Kupffer cells injured neither sinusoidal endothelial cells nor hepatocytes. The activity of tissue factor, an initiator of blood coagulation cascade, was much higher in Kupffer cells isolated from partially hepatectomized rats than in those from normal rats. In contrast, mRNA expressions of tissue factor pathway inhibitor (TFPI) as well as thrombomodulin were almost undetectable in normal and partially resected livers. When recombinant human TFPI was injected intravenously in 70% hepatectomized rats, TFPI was markedly stained on the surfaces of sinusoidal endothelial cells and microvilli of hepatocytes on immunohistochemistry. In these rats, endotoxin-induced liver injury was significantly attenuated compared with rats given no TFPI. Similar attenuation was also found in rats receiving recombinant human thrombomodulin. These results suggest that fibrin deposition developing in 70% hepatectomized rats after endotoxin administration may be caused by deranged blood coagulation in the hepatic sinusoids through increasing tissue factor activity in Massive liver necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes or those undergoing 70% liver resection as a result of microcirculatory disturbance caused by sinusoidal fibrin deposition. [1][2][3] In both models, Kupffer cells and hepatic macrophages are activated to provoke endothelial cell injury and fibrin deposition in the hepatic sinusoids. 2-6 However, an apparent difference exists in the stimulatory state of Kupffer cells and hepatic macrophages between both models, because activated Kupffer cells in the partial-hepatectomy model produced fewer cytotoxic mediators such as superoxide anions and tumor necrosis factor ␣ in response to endotoxin administration compared with activated hepatic macrophages in the P. acnes model, 6,7 although both cells can release a large amount of superoxide anions after stimulation with phorbol 12-myristate 13-acetate. 3,4 Northern blot analysis revealed that such difference resulted from expression of endotoxin receptors on the cells; P. acnes-treated rat liver showed increased mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, compared with normal liver, while such expression was markedly reduced in partially hepatectomized rat liver. 7 In the P. acnes model, activated hepatic macrophages after endotoxin stimulatio...

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Involvement of tumor necrosis factor-α in the pathogenesis of activated macrophage-mediated hepatitis in mice

Cited by 125 publications

References 26 publications

How valid is emergency liver transplantation for acute liver necrosis in patients with multiple-organ failure?

How valid is emergency liver transplantation for acute liver necrosis in patients with multiple-organ failure?

FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion

Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats

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