A sublethal dose of LPS to pregnant rats induces TNF-alpha tolerance in their 0-day-old offspring

Gotō, Masakatsu; Yoshioka, Toshimasa; Young, Rita I.; Battelino, Tadej; Anderson, Christopher L.; Zeller, W. P.

doi:10.1152/ajpregu.1997.273.3.r1158

Cited by 7 publications

(13 citation statements)

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“…A B tioned above, the ip route, under the present experimental circumstances, proved to be totally inadequate for the rat C. hepatica model. It is well known that not only the doses but also the route of administration of antigens have considerable effects on the immune response (17)(18)(19)(20). Also, for the process of immunological tolerance it is important that the antigens remain for a prolonged period of time within the organism, otherwise only a transient tolerance would be induced (21).…”

Section: Discussionmentioning

confidence: 99%

Immunological basis of septal fibrosis of the liver in Capillaria hepatica-infected rats

Lemos

Magalhães-Santos

Andrade

2003

Braz J Med Biol Res

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Rats infected with the helminth Capillaria hepatica regularly develop septal fibrosis of the liver similar to that induced by repeated ip injections of pig serum. Fibrosis starts when the focal parasitic lesions begin to show signs of resorption, thus suggesting an immunologically mediated pathogenesis of this fibrosis. To explore this possibility, the development of C. hepatica-related hepatic fibrosis was observed in rats exposed to worm antigens from the first neonatal day onward. Wistar rats (150 g) were either injected ip with an extract of C. hepatica eggs (protein concentration: 1 mg/ml) or received immature eggs by gavage from the first neonatal day until adult life and were then infected with 500 embryonated eggs. Changes were monitored on the basis of serum levels of anti-worm antibodies and hepatic histopathology. Rats submitted to immunological oral tolerance markedly suppressed C. hepatica-related serum antibodies and septal fibrosis of the liver when infected with the helminth later on. Tolerance trials with ip injections of worm antigens gave essentially negative results. The partial suppression of septal fibrosis of the liver after the induction of immunological tolerance to C. hepatica antigens in rats indicates an immunological basis for the fibrosis and emphasizes the importance of immunological factors in the pathogenesis of hepatic fibrosis.

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Section: Discussionmentioning

confidence: 99%

Immunological basis of septal fibrosis of the liver in Capillaria hepatica-infected rats

Lemos

Magalhães-Santos

Andrade

2003

Braz J Med Biol Res

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“…Endotoxin [lipopolysaccharide (LPS)], a component of the outer cell membranes of gram-negative bacteria, is thought to be responsible for gram-negative septic shock. A large dose of LPS causes hemodynamic and metabolic derangements resulting in shock and death [1]. However, a small dose of LPS can induce hyporesponsiveness to LPS [1].…”

Section: Introductionmentioning

confidence: 99%

“…A large dose of LPS causes hemodynamic and metabolic derangements resulting in shock and death [1]. However, a small dose of LPS can induce hyporesponsiveness to LPS [1]. This hyporesponsiveness is characterized by decreased response of body temperature to LPS and by decreased mortality in response to a second injection of LPS [2].…”

Section: Introductionmentioning

confidence: 99%

“…Early endotoxin tolerance is not due to the production of antibodies but rather to an altered macrophage response to LPS, decreasing phago-cyte activity and tumor necrosis factor alpha (TNF-·) production [5,6]. The hyporesponsiveness which develops is not only to the LPS injected for the induction but also to other LPSs [1]. These results suggest that early endotoxin tolerance is not LPS-specific.…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic Treatment of Endotoxic Shock with Monophosphoryl Lipid A in Newborn Rats

Gotō

Young

et al. 2000

Neonatology

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Mortality due to gram-negative septic shock remains high despite advances in medical care. Induction of endotoxin tolerance might be a new treatment strategy to prevent septic shock in the newborn. The present study was performed to show that an injection in pregnant rats of monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide (LPS), induces tolerance to Salmonella enteritidis LPS and tumor necrosis factor alpha (TNF-α) in their offspring. MPL at a dose of 2 mg/kg was injected into pregnant rats on the 19th day of gestation. Their 0-day-old offspring later received an intraperitoneal injection of S. enteritidis LPS or TNF-α. Newborn rats of MPL-treated dams exhibited a higher survival rate, absence of lactacidemia and lower plasma TNF-α concentration in response to S. enteritidis LPS when compared to the newborn rats of saline-treated dams. Newborn rats of MPL-treated dams were more tolerant to TNF-α than those of saline-treated dams. MPL injection into pregnant rats did not increase plasma endotoxin concentration in the fetuses, suggesting no placental passage took place, but it did increase plasma TNF-α concentration. We concluded that an injection of MPL into pregnant rats induced tolerance to LPS in their offspring, which might be due to TNF-α-induced TNF-α tolerance.

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“…Under these conditions and dependent on the presence of TNFR1 (10), TNF induces apoptotic liver damage, which is characterized by the formation of mitochondrial permeability transition pores, release of cytochrome c, as well as by the activation of caspases (11)(12)(13). Contrarily, pretreatment with TNF alone, without transcriptional inhibition, for 2 to at least 24 h protects mice from apoptotic liver damage subsequently induced by GalN/TNF application (14,15). Concerning mechanisms of protection, it has been shown, that, similar to TNF preconditioning in hepatic ischemia-reperfusion injury, protection in the GalN/TNF model is dependent on TNF/ TNFR1 interaction (16).…”

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confidence: 99%

TNF Pretreatment Interferes with Mitochondrial Apoptosis in the Mouse Liver by A20-Mediated Down-Regulation of Bax

Sass

Shembade

Haimerl

et al. 2007

The Journal of Immunology

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Pretreatment with low doses of the proinflammatory cytokine TNF has been shown to prevent hepatocellular apoptosis and liver damage in inflammatory as well as in ischemia/reperfusion-induced liver injury. The underlying mechanisms of protection have not been elucidated so far. In this study, these mechanisms were investigated in murine hepatocyte cultures as well as in a mouse model of TNF-dependent apoptotic liver damage (galactosamine/TNF model). Our results show that pretreatment with TNF, or application of small-interfering RNA directed against the proapoptotic Bcl2 family member Bax, interfered with the onset of mitochondrial apoptosis in vivo. Knockdown of TNF-α-induced-protein 3 (A20) restored mitochondrial apoptosis, Bax expression, and liver damage. The underlying mechanism of protection seems to involve a cascade of events, where TNF induces the expression of A20 in hepatocytes, A20 down-modulates Bax expression by interference with transcriptional activation, and the reduced availability of Bax interferes with the onset of mitochondrial apoptosis and the ensuing apoptotic liver damage. In conclusion, we identified Bax and A20 as key players in TNF-induced protection from apoptotic liver damage. Because treatment with TNF itself might be a risk factor for patients, we propose that overexpression of A20 might represent an alternative approach for protection from inflammation related apoptotic liver damage, as well as for TNF preconditioning during transplantation.

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A sublethal dose of LPS to pregnant rats induces TNF-alpha tolerance in their 0-day-old offspring

Cited by 7 publications

References 0 publications

Immunological basis of septal fibrosis of the liver in Capillaria hepatica-infected rats

Immunological basis of septal fibrosis of the liver in Capillaria hepatica-infected rats

Prophylactic Treatment of Endotoxic Shock with Monophosphoryl Lipid A in Newborn Rats

TNF Pretreatment Interferes with Mitochondrial Apoptosis in the Mouse Liver by A20-Mediated Down-Regulation of Bax

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