Possible Endotoxemia in Rabbits after Intravenous Injection of Staphylococcus aureus Enterotoxin B

Pettit, George W; Elwell, Michael R.; Jahrling, Peter B.

doi:10.1093/infdis/135.4.646

Cited by 24 publications

(15 citation statements)

References 8 publications

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“…In studies on rabbits, 47 we found that iv injection of SEB resulted in appearance of appreciable levels (up to 1 /ig/ml) of endotoxin in plasma, presumably absorbed from the gut; death was associated with endotoxemia, and survival was associated with lack of endotoxemia. In the present study we obtained contrasting results in that endotoxin never was detectable in any of the monkeys despite measurement at repeated time intervals during enterotoxemia.…”

Section: Endotoxinmentioning

confidence: 85%

Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors.

Pettit¹,

Yamada²,

Wing³

et al. 1978

Circulation Research

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SUMMARY Staphylococcal enterotoxin B, a protein exotoxin from Staphylococcus aureus, produced progressive hypotension and shock when injected (1 mg/kg, iv) into rhesus monkeys. Plasma levels of factors which have been implicated in the pathogenesis of other types of shock were measured. Endotoxin-like activity was measured by the Limulus lysate technique, fibrin degradation products (FDP) were quantified by electroimmunoassay, and activation of the complement system was assayed by measuring total hemolytic complement. Activation of the intrinsic coagulation cascade was assessed by measuring activated partial thromboplastin time (APTT). Activation of the kinin system was evaluated by measuring prekallikrein activity and kininogen. Myocardial depressant factor (MDF) was measured by paper chromatography. Endotoxin-like activity did not appear in plasma, and the complement system was not activated. The appearance of FDP and a significant trend for prolongation of APTT indicated activation of fibrinolysis and the intrinsic coagulation cascade, and suggested that disseminated intravascular coagulation was occurring. Activation of the kinin system was shown by a progressive and significant depletion of kininogen from 338 ± 37 to 226 ± 22 ng kallidin generated/ml, and a significant depletion of plasma prekallikrein activity from 169 ± 8 to 110 ± 15 tosyl arginine methyl ester (TAMe) esterase U/ml. Analysis of covariance indicated that activation of the kinin system was related to changes in blood pressure. MDF did not increase until immediately before death (increase from 1.08 ± 0.15 to 1.92 ± 0.11 paper chromatographic U//tl, n = 6). We conclude that kinins, MDF, and disseminated intravascular coagulation, but not complement or endotoxin, may contribute to the pathogenesis of enterotoxic shock in rhesus monkeys.ENTEROTOXINS isolated from cultures of Staphylococcus aureus are protein exotoxins (28,000-29,000 daltons, molecular weight) which are capable of producing acute food poisoning in humans 1 and other primates.2 Intravenous (iv) injection of enterotoxins in very small doses in rabbits and monkeys produces lethargy, fever, shock, and death.3 There is evidence that during staphylococcal wound infections and purulent skin lesions, enough enterotoxin is released into the circulation of an infected patient to stimulate synthesis of antibody specific to the toxins produced. 4 Since circulating enterotoxins might contribute to the hypotension and shock often observed in these patients, we decided to study possible mechanisms by which enterotoxin causes circulatory shock.When Josefczyk 4 measured anti-enterotoxin antibodies in normal patients and patients with staph- ylococcal infections, antibody to staphylococcal enterotoxin type B (SEB) was the most common type in each group. SEB has been isolated in purity greater than 99%, 5 and its amino acid sequence has been determined. 6 To help to elucidate the mechanisms by which enterotoxins produce shock, we injected SEB (1 mg/kg, iv) into rhesus monkeys and measured plasma l...

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Section: Endotoxinmentioning

confidence: 85%

Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors.

Pettit¹,

Yamada²,

Wing³

et al. 1978

Circulation Research

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“…The values represent the mean ϩ SD for duplicate samples from three experiments. Numerous investigations show that LPS potentiates the biologic effects of SEs and that septic shock may reflect a culmination of excessive proinflammatory cytokines resulting from the actions of both toxins (3,4,24,35,39,40,42). Although SE and LPS often lead to different sequelae, acute shock caused by abnormally high levels of TNF-␣ and other proinflammatory cytokines results in life-threatening situations (8,11,38).…”

Section: Fig 2 Levels Of Tnf-␣ (A) Ifn-␥ (B) Il-1␣ (C)mentioning

confidence: 99%

Pirfenidone Blocks the In Vitro and In Vivo Effects of Staphylococcal Enterotoxin B

Hale

Margolin²,

Krakauer

et al. 2002

Infect Immun

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Pirfenidone [5-methyl-1-phenyl-2-(1H)-pyridone] down-regulates expression of cytokines and other mediators involved in the onset and development of pulmonary fibrosis. Pirfenidone also inhibits production of tumor necrosis factor alpha (TNF-␣) from macrophages incubated with endotoxin and protects mice against endotoxin shock. Pirfenidone's ability to reduce cytokine expression in these disorders led us to investigate the drug's effect on another cytokine anomaly, superantigen-induced shock. BALB/c mice were exposed to staphylococcal enterotoxin B (SEB) either systemically or by aerosol and subsequently potentiated with a sublethal dose of lipopolysaccharide. In these experiments, pirfenidone given 2 to 4.25 h after SEB resulted in 80 to 100% survival versus only 0 to 10% survival among untreated control animals. Relative to serum cytokine levels from controls given toxin but no drug, there was a 35 to 80% decrease in TNF-␣, interleukin 1, and other proinflammatory cytokines. In vitro experiments with human peripheral blood lymphocytes revealed that pirfenidone reduced SEB-induced cytokine levels 50 to 80% and inhibited 95% of SEB-induced T-cell proliferation. Overall, these studies demonstrated the potential utility of pirfenidone as a therapeutic against septic shock and the biological effects of SEB.

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“…As evidenced in mice with the various staphylococcal superantigens, different rabbit strains also possess varying susceptibility toward TSST-1 as New Zealand whites are more susceptible vs. Dutch belted 113 . As witnessed in humans with toxic shock, rabbits given TSST-1 or SEB experience elevated levels of circulating LPS eliminated by polymyxin B 113 , 114 . From a biodefense perspective, intrabronchial instillation of SEB (SEC or TSST-1 too) into rabbits can be useful for testing potential therapies and vaccines 115 .…”

Section: In Vivo Effects: Animal Models and Morementioning

confidence: 99%

The staphylococcal enterotoxin (SE) family

Krakauer

Stiles

2013

Virulence

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Staphylococcus aureus plays an important role in numerous human cases of food poisoning, soft tissue, and bone infections, as well as potentially lethal toxic shock. This common bacterium synthesizes various virulence factors that include staphylococcal enterotoxins (SEs). These protein toxins bind directly to major histocompatibility complex class II on antigen-presenting cells and specific Vβ regions of T-cell receptors, resulting in potentially life-threatening stimulation of the immune system. Picomolar concentrations of SEs ultimately elicit proinflammatory cytokines that can induce fever, hypotension, multi-organ failure, and lethal shock. Various in vitro and in vivo models have provided important tools for studying the biological effects of, as well as potential vaccines/therapeutics against, the SEs. This review succinctly presents known physical and biological properties of the SEs, including various intervention strategies. In particular, SEB will often be portrayed as per biodefense concerns dating back to the 1960s.

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Possible Endotoxemia in Rabbits after Intravenous Injection of Staphylococcus aureus Enterotoxin B

Cited by 24 publications

References 8 publications

Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors.

Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors.

Pirfenidone Blocks the In Vitro and In Vivo Effects of Staphylococcal Enterotoxin B

The staphylococcal enterotoxin (SE) family

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