Endogenous versus exogenous glucocorticoid responses to experimental bacterial sepsis

Silverstein, Richard; Johnson, Donald C.

doi:10.1189/jlb.0702379

Cited by 19 publications

(21 citation statements)

References 98 publications

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“…Thus, as in those studies described above, adrenalectomy enhanced lethality from Gram-negative bacteria, such as E. coli, and this could be reversed by dexamethasone treatment (Silverstein & Johnson 2003). However, dexamethasone treatment did not prevent the mildly enhanced lethality from the Grampositive bacterium S. aureus in adrenalectomized animals (Silverstein & Johnson 2003). In a -galactosamine mouse model of septic shock, dexamethasone prevented lethality in all 10 Gram-negative strains tested but in only three (Enterococcus faecalis) of the 11 Gram-positive strains tested (Papasian et al 2002).…”

Section: Live Bacteriasupporting

confidence: 60%

“…In these experiments, the effects of adrenalectomy in enhancing mortality and the protective efficacy of dexamethasone in preventing this effect vary with bacterial strain and type. Thus, as in those studies described above, adrenalectomy enhanced lethality from Gram-negative bacteria, such as E. coli, and this could be reversed by dexamethasone treatment (Silverstein & Johnson 2003). However, dexamethasone treatment did not prevent the mildly enhanced lethality from the Grampositive bacterium S. aureus in adrenalectomized animals (Silverstein & Johnson 2003).…”

Section: Live Bacteriamentioning

confidence: 59%

“…For example, antibiotics in combination with dexamethasone protect against S. aureus whereas dexamethasone alone was ineffective (Silverstein et al 2000, Silverstein & Johnson 2003. This difference between dexamethasone alone and dexamethasone in conjunction with antibiotic treatment is probably due to the release of bacterial products during antibiotic bacterial death, which in some cases may induce a different cytokine pattern (Cui et al 2000, 2003, Silverstein et al 2000.…”

Section: Live Bacteriamentioning

confidence: 99%

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Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Webster

Sternberg

2004

Journal of Endocrinology

164

124

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The hypothalamic-pituitary-adrenal (HPA) axis is activated during many bacterial and viral infections, resulting in an increase in circulating glucocorticoid levels. This HPA axis activation and glucocorticoid response are critical for the survival of the host, as demonstrated by the fact that removal of the HPA axis (by adrenalectomy or hypophysectomy) or glucocorticoid receptor (GR) blockade enhances the severity of the infection and in some cases enhances the mortality rate. Replacement with a synthetic glucocorticoid reverses these effects by reducing the severity of the infection and provides protection against lethal effects. In addition, some bacteria and viral infections have been shown to affect the GR directly. These have been described and the implications of such an effect discussed.

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Section: Live Bacteriasupporting

confidence: 60%

Section: Live Bacteriamentioning

confidence: 59%

Section: Live Bacteriamentioning

confidence: 99%

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Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Webster

Sternberg

2004

Journal of Endocrinology

164

124

View full text Add to dashboard Cite

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“…4). This is in agreement with a previous report showing that glucocorticoid treatment was effective at protection against E. coli but not so good in the case of S. aureus infection (36). These observations suggest that the enhanced resistance induced by stress or the use of glucocorticoids (corticotherapy) to sepsis may be specific to some species of pathogens.…”

Section: Discussionsupporting

confidence: 92%

Enhanced Resistance of Restraint-Stressed Mice to Sepsis

Wang

Lü

et al. 2008

The Journal of Immunology

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Sepsis remains a major health concern across the world. The effects of stress on host resistance to sepsis are still not very clear. To explore the effects of chronic stress on sepsis’ we examined the impact of restraint stress on the resistance of mice to sepsis. Interestingly, it was found that restraint stress enhanced the antisepsis resistance of mice and the concentrations of the proinflammatory cytokines IL-1, IL-6, IL-12, and TNF-α in the blood of stressed mice were dramatically reduced post Escherichia coli infection or LPS treatment as compared with that of controls (p < 0.05). In addition, the mRNA expressions of glucocorticoid-induced leucine zipper (GILZ) were up-regulated in the spleen and peritoneal macrophages of mice receiving restraint stress or dexamethasone treatment. These results demonstrate that restraint stress enhances the resistance of mice to sepsis, supporting corticotherapy for sepsis and proposing restraint-stressed mouse as an animal model to elucidate mechanisms of stress-associated, antisepsis resistance.

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“…35 By contrast, dexamethasone protection is now potentiated following antibiotic treatment in the D-galN model, both among CF-1 mice and C3H/HeJ mice. 36 Given the Gram-negative and Gram-positive bacterial components that contribute to lethality in D-galN-sensitized mice, it will be of some interest to know the impact of antibiotic killing on the ability of other agents, extrapolating from dexamethasone, to protect against lethality.…”

Section: Mechanisms Of Lps Lethality In Normal Versus D-galnsensitizementioning

confidence: 99%

Review: D-Galactosamine lethality model: scope and limitations

Silverstein

2004

Journal of Endotoxin Research

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INTRODUCTIONGalanos and coworkers published two reports, one in 1979 and the other in 1987, that together provided the framework for more than 250 papers from a variety of laboratories using D-galactosamine (D-galN) as a sensitizing agent to TNF-mediated lethality. 1,2 Included in those initial reports, it was established that administration of D-galN in sufficient dose and at the same time as either LPS or TNF was able to reduce the LD 50 value for LPS and for TNF by several orders of magnitude (see below). Complete protection was afforded by anti-TNF neutralizing antibody establishing that lethality from LPS in this model resulted exclusively from sensitization to the lethal effects of TNF, a particularly seminal finding. 3 Administration of uridine at the time of challenge also completely protected against lethality. It was further established, most definitively from adoptive transfer experiments, that in the D-galN model of LPS lethality, endotoxin responsive macrophages were essential, 1,2,4-6 as is also recognized to be the case for LPS lethality in unsensitized mice. 7 While it is otherwise conceivable that D-galN might sensitize to lethality not only by increasing sensitivity to TNF but also by increasing TNF levels, D-galN does not, of itself, appreciably change circulating levels of TNF following challenge with LPS. 8 Dramatic sensitization to LPS lethality brought on by a simple amino sugar is unique to D-galN. Other chemical agents, such as lead acetate, actinomycin D, among others, are also potent at sensitizing to LPS lethality. 9-12 D-galN is, nevertheless, unique among these in that it is naturally occurring in the host, and sensitizes in a welldefined time period after its administration, by a welldefined metabolic mechanism, and by a well-defined cytokine mechanism, namely via TNF. With respect to the metabolic mechanism, it has been established that the same enzyme machinery that converts glucose to UDP-glucose and galactose to UDP-galactose also con- (D-galN) is well established as sensitizing mice and other animals to the lethal effects of TNF, specifically, and by several orders of magnitude. Protection by anti-TNF neutralizing antibody is complete, as is (metabolically-based) protection by uridine. Sensitization occurs regardless of the origin of the released TNF, whether it is released from macrophages and/or T-cells. The same is true for the challenging agent which leads to the release of TNF, whether it is endotoxin, a superantigen, lipoprotein, bacterial DNA, or bacteria, either killed or proliferating. Most studies have utilized endotoxin as the challenging agent, and more than 70 agents have been reported to confer protection against LPS and/or TNF challenge in the model. The model has provided new insight regarding modes of protection, including from dexamethasone, which protects against challenge from LPS but not from challenge by TNF. The D-galN lethality model has also been used to test for synergistic behavior between different bacterial components, and to test for lethality wh...

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Endogenous versus exogenous glucocorticoid responses to experimental bacterial sepsis

Cited by 19 publications

References 98 publications

Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Enhanced Resistance of Restraint-Stressed Mice to Sepsis

Review: D-Galactosamine lethality model: scope and limitations

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