Lethal Staphylococcus Aureus-Induced Shock in Primates

Hinshaw, Lerner B.; Emerson, Thomas E.; Taylor, Fletcher B.; Chang, Alvin; Duerr, M; Peer, G.; Flournoy, Dale J.; White, Gary L.; Kosanke, Stanley D.; Murray, Cynthia K.; Xu, Renfeng; Passey, Richard B.; Fournel, Michael A.

doi:10.1097/00005373-199210000-00013

Cited by 122 publications

(51 citation statements)

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“…Clearly the TNF-␣ levels observed following LPD injection approach those which are observed with toxic shock syndrome. [43][44][45] Indeed, a future challenge is to harness the antitumor activity of LPD to direct specific immunity against certain types of cancer. …”

Section: Discussionmentioning

confidence: 99%

LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth

1999

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Our laboratory has recently developed a lipopolyplex response required assembly of DNA into a lipoplex or the consisting of DOTAP:cholesterol liposomes, protamine LPD lipopolyplex. Except for the heart, elevated levels of sulfate, and plasmid DNA (LPD) that provides improved cytokine were observed in all organs (lung, liver, kidney systemic gene delivery compared with lipoplex following and spleen) where LPD is known to have gene transfer tail vein injection in mice. Because endothelial cells are the activity. Methylation of immune-stimulatory CpG motifs in primary cells transfected in the lung, it was hypothesized the plasmid component of LPD inhibited the proinflammathat LPD might be an effective vector for gene therapy of tory cytokine response as well as the antitumor effect of pulmonary metastases. This hypothesis was examined by LPD in both tumor systems. This suggests that i.v. administesting the efficacy of cytokine (IL-12) and tumor suptration of LPD elicits a systemic proinflammatory cytokine pressor (p53) strategies for treatment of an experimental response that mediates the antitumor activity of the lipopomodel of pulmonary metastasis in C57Bl/6 mice. Surprislyplex. In addition, the antitumor activity was not observed ingly, all LPD complexes including those containing an in SCID mice suggesting a possible role for B or T lympho-'empty' plasmid provided a potent (Ͼ50% inhibition) and cytes in the antitumor response initiated by LPD. This repdose-dependent antitumor effect, compared with dextroseresents the first demonstration that an intravenously treated controls. In addition, i.v. injections of LPD containadministered cationic liposome-based nonviral vector can ing 'empty' plasmid also inhibited tumor growth in a subcutpromote a systemic, Th1-like innate immune response. aneous model of C3 fibrosarcomma. The antitumor effectThe immune adjuvant properties of LPD might prove to be correlated well with a strong and rapid proinflammatory suitable for delivering tumor-specific antigens in the context cytokine (TNF-␣, IL-12 and IFN-␥) response. Naked plasof DNA vaccination. mid DNA did not elicit a cytokine response and the

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Section: Discussionmentioning

confidence: 99%

LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth

1999

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“…Hence, the production of pro-in¯ammatory mediators, mainly the cytokines tumour necrosis factor (TNF)-a, interleukin (IL)-1b and interferon (IFN-g)-g, in the infectious focus is important in the recruitment and activation of leukocytes, key events in restricting the spread of infection (Hinshaw et al, 1992;Zhao et al, 1998). However, the overproduction of these mediators in the circulation results in SIRS, which culminates in morbidity and/or mortality of the individual (Walley et al, 1996;Bone et al, 1997;Martineau & Shek, 2000).…”

Section: Introductionmentioning

confidence: 99%

Involvement of NO in the failure of neutrophil migration in sepsis induced by Staphylococcus aureus

Crosara-Alberto

Darini

Inoue

et al. 2002

British J Pharmacology

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Sepsis induced by S. aureus was used to investigate whether neutrophil migration failure to infectious focus correlates with lethality in Gram‐positive bacteria‐induced sepsis in mice. By contrast with the sub‐lethal (SL‐group), the lethal (L‐group) intraperitoneal inoculum of S. aureus caused failure of neutrophil migration (92% reduction), high CFU in the exudate, bacteremia and impairment of in vitro neutrophil chemotactic activity. Pre‐treatments of L‐group with adequate doses of aminoguanidine prevented the neutrophil migration failure and improved the survival of the animals (pre‐treated: 43%; untreated: 0% survival). Thus, the impairment of neutrophil migration in the L‐group appears to be mediated by nitric oxide (NO). The injection of S. aureus SL‐inoculum in iNOS deficient (−/−) or aminoguanidine‐treated wild‐type mice (pre‐ and post‐treatment), which did not present neutrophil migration failure, paradoxically caused severe peritonitis and high mortality. This fact is explainable by the lack of NO dependent microbicidal activity in migrated neutrophils. In conclusion, although the NO microbicidal mechanism is active in neutrophils, the failure of their migration to the infectious focus may be responsible for the severity and outcome of sepsis. British Journal of Pharmacology (2002) 136, 645–658; doi:10.1038/sj.bjp.0704734

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“…TNF-␣ also contributes significantly to multiple-organ failure, shock, and death resulting from challenge with purified gram-positive bacterial components (e.g., peptidoglycan), as well as with live or heat-killed gram-positive organisms (7,10,13,19). Conversely, the possibility exists that under some circumstances TNF-␣ will be beneficial to recovery from sepsis.…”

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Differential Host Inflammatory Responses to Viable Versus Antibiotic-Killed Bacteria in Experimental Microbial Sepsis

Silverstein¹,

Wood

Xue

et al. 2000

Infect Immun

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Staphylococcus aureus killed during imipenem or ceftazidime chemotherapy in mice elicited an early release of tumor necrosis factor alpha (TNF-␣) into the systemic circulation. This response was coincident in time with an increase in leukocyte-endothelium adhesive interactions in the microvasculature. Equivalent responses were not observed without the antibiotic treatment (imipenem or ceftazidime). Protective efficacy of the same antibiotic treatment was markedly diminished in D-galactosamine-treated mice compared to controls; e.g., it dropped from 2,000-fold to 70-fold with 4 mg of imipenem per kg given at the time of challenge. Nevertheless, protection was quantitatively restored upon concurrent administration of neutralizing anti-TNF-␣ antibody or 4 mg of dexamethasone per kg to these TNF-␣-hypersensitive mice. Importantly, protection afforded by dexamethasone was not seen when the animals were challenged with viable organisms but without the concurrent administration of antibiotic. An early TNF-␣ response could also be demonstrated upon challenge with Escherichia coli, but in this instance, neither the timing nor the magnitude of that response was influenced by treatment with these antibiotics. We conclude from these studies that the inflammatory response to viable versus killed bacteria may differ markedly depending on the particular bacterium, host sensitivity to TNF-␣, and possibly the Gram stain classification.

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Lethal Staphylococcus Aureus-Induced Shock in Primates

Cited by 122 publications

References 0 publications

LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth

LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth

Involvement of NO in the failure of neutrophil migration in sepsis induced by Staphylococcus aureus

Differential Host Inflammatory Responses to Viable Versus Antibiotic-Killed Bacteria in Experimental Microbial Sepsis

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