scholarly journals Comparable Endotoxic Properties of Lipopolysaccharides Are Manifest in Diverse Clinical Isolates of Gram-Negative Bacteria

2000 ◽  
Vol 68 (4) ◽  
pp. 1899-1904 ◽  
Author(s):  
Michael Luchi ◽  
David C. Morrison
Keyword(s):  
Biologically Active ◽  
Clinical Isolates ◽  
Poor Correlation ◽  
Gram Negative Bacteria ◽  
Active Constituent ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Factor Alpha ◽  
Phenol Water ◽  
Necrosis Factor

ABSTRACT In general there is a poor correlation between serum lipopolysaccharide (LPS; the biologically active constituent of endotoxin) levels and mortality in septic patients. The objective of this study was to determine if chemical, structural, or biological differences among LPS from different clinical isolates of gram-negative bacteria might explain this discrepancy. LPS preparations were made using the hot phenol-water extraction method from eight clinical isolates of gram-negative bacteria. As a percentage of the total weight of the LPS, the phosphate content ranged from 3.0 to 13.8% (average, 6.7 ± 3.6%), and the 2-keto-3-deoxyoctonate content ranged from 1.9 to 27.4% (average, 8.9 ± 8.5%). These values were not dissimilar to those obtained for a reference endotoxin. In a standard measure of LPS activity, the Limulus amoebocyte lysate assay, there was approximately a twofold difference between the least and most active preparations. The two preparations with the greatest difference in their ability to elicit the secretion of tumor necrosis factor alpha from a mouse peritoneal macrophage cell line were similar in lethality when administered to mice sensitized to the effects of LPS by d(+)-galactosamine. These relatively minor differences in LPS activity seem unlikely to explain the generally observed discrepancy between serum endotoxin levels and mortality in patients with gram-negative sepsis.

scholarly journals Bacterial endotoxins: biological properties and mechanisms of action

1993 ◽  
Vol 2 (7) ◽  
pp. S11-S16 ◽  
Author(s):  
C. Galanos ◽  
M. A. Freudenberg
Keyword(s):  
Biological Properties ◽  
Mechanisms Of Action ◽  
Review Article ◽  
Gram Negative Bacteria ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Lethal Action ◽  
Bacterial Endotoxins ◽  
Factor Alpha ◽  
Necrosis Factor

Endotoxins (lipopolysaccharides, LPS) are agents of pathogenicity of Gram-negative bacteria, implicated in the development of Gram-negative shock. Endotoxin reacts with lipopolysaccharide-sensitive cells producing endogenous mediators such as tumour necrosis factor alpha (TNFα). Macrophages are cells mediating the toxic activities of LPS and TNFα is the primary mediator of the lethal action of endotoxin. This review article discusses the various mechanisms by which endotoxin hypersensitivity in bacteria-sensitized animals develops. The paper concludes with a discussion on the possible protective effect of carnitine congeners against the lethal action of LPS.

scholarly journals Comparative Effects of Ciprofloxacin and Ceftazidime on Cytokine Production in Patients with Severe Sepsis Caused by Gram-Negative Bacteria

2004 ◽  
Vol 48 (8) ◽  
pp. 2793-2798 ◽  
Author(s):  
C. A. Gogos ◽  
A. Skoutelis ◽  
A. Lekkou ◽  
E. Drosou ◽  
I. Starakis ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Group Versus ◽  
Gram Negative Bacteria ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT In the present study the effect of ciprofloxacin versus ceftazidime on concentrations of pro- and anti-inflammatory cytokines in the sera of patients with severe sepsis was evaluated. The study included 58 previously healthy patients suffering from severe sepsis caused by gram-negative bacteria, treated with either ciprofloxacin or ceftazidime after thorough clinical and microbiological evaluation and followed up for clinical outcome. Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1b (IL-1b), IL-6, and IL-8 and of the anti-inflammatory cytokine IL-10, as well as of IL-1 receptor antagonist and soluble TNF receptors I and II, in serum were measured at baseline and 24 and 48 h after the first antimicrobial dose. Mean SAPS-II scores, development of septic shock, and mortality rates were similar in the two groups (43.2 ± 9.2, 21.4%, and 14.3% in the ceftazidime group versus 49.8 ± 11.3, 20%, and 13.3% in the ciprofloxacin group). Serum TNF-α and IL-6 levels at 24 and 48 h were significantly lower in the ciprofloxacin group, while the IL-10/TNF-α ratio was significantly higher, than those for the ceftazidime group. Among patients with high baseline TNF-α levels, there were significant increases in the IL-10/TNF-α ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group. These results indicate that ciprofloxacin may have an immunomodulatory effect on septic patients by attenuating the proinflammatory response, while there is no evidence that differences in the cytokines measured have any impact on the final outcome.

scholarly journals Phagocytic and Tumor Necrosis Factor Alpha Response of Human Mast Cells following Exposure to Gram-Negative and Gram-Positive Bacteria

1998 ◽  
Vol 66 (12) ◽  
pp. 6030-6034 ◽  
Author(s):  
Michel Arock ◽  
Elaine Ross ◽  
René Lai-Kuen ◽  
Geneviève Averlant ◽  
Zhimin Gao ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Human Mast Cells ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Recent studies have implicated rodent mast cells in the innate immune response to infectious bacteria. We report that cord blood-derived human mast cells (CBHMC) obtained from culture of cord blood progenitors phagocytozed and killed various gram-negative and gram-positive bacteria and simultaneously released considerable amounts of tumor necrosis factor alpha. Overall, the extent of the endocytic and exocytic response of CBHMC correlated with the number of adherent bacteria. Thus, human mast cells are intrinsically capable of mediating microbial recognition and of actively contributing to the host defense against bacteria.

scholarly journals Recombinant Bactericidal/Permeability-Increasing Protein rBPI21 Protects against Pneumococcal Disease

2006 ◽  
Vol 75 (1) ◽  
pp. 342-349 ◽  
Author(s):  
Amit Srivastava ◽  
Heather Casey ◽  
Nathaniel Johnson ◽  
Ofer Levy ◽  
Richard Malley
Keyword(s):  
Pneumococcal Disease ◽  
Gram Negative Bacteria ◽  
Dependent Manner ◽  
Upper Respiratory Tract ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Murine Macrophages ◽  
Mouse Macrophages ◽  
Factor Alpha ◽  
Potential Interactions

ABSTRACT Bactericidal/permeability-increasing (BPI) protein has been shown to play an important role in innate immunity to gram-negative bacteria, by direct microbicidal as well as endotoxin-neutralizing action. Here we examined potential interactions between a recombinant 21-kDa bioactive fragment of BPI, rBPI21, and the gram-positive pathogen Streptococcus pneumoniae. rBPI21 bound to pneumococci and pneumolysin (Ply) in a direct and specific fashion. We observed an enhanced inflammatory response in mouse macrophages when rBPI21 was combined with killed pneumococci or supernatant from overnight growth of pneumococci. In addition, rBPI21 augmented the proapoptotic activity of Ply+ (but not Ply−) pneumococci in TLR4-defective murine macrophages (known to be defective also in their apoptotic response to pneumolysin) in a tumor necrosis factor alpha-dependent manner. rBPI21 also enhanced the association of pneumococci with murine macrophages. In a model of invasive pneumococcal disease in TLR4-defective mice, the intranasal administration of rBPI21 following intranasal inoculation of Ply+ pneumococci both enhanced upper respiratory tract cell apoptosis and prolonged survival. We have thus discovered a novel interaction between pneumococcus and rBPI21, a potent antimicrobial peptide previously considered to target only gram-negative bacteria.

scholarly journals Differential Tumor Necrosis Factor Alpha Expression and Release from Peritoneal Mouse Macrophages In Vitro in Response to Proliferating Gram-Positive versus Gram-Negative Bacteria

2000 ◽  
Vol 68 (8) ◽  
pp. 4422-4429 ◽  
Author(s):  
Wei Cui ◽  
David C. Morrison ◽  
Richard Silverstein
Keyword(s):  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
E Coli ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.

scholarly journals Διαφορές και ομοιότητες στην ανοσιακή απάντηση του σηπτικού ασθενούς μετά οξεία χειρουργική κοιλία συγκριτικά με το σηπτικό σύνδρομο άλλης λοιμώδους αιτιολογίας

2014 ◽  
Author(s):  
Ιωάννης Κριτσέλης
Keyword(s):  
Severe Sepsis ◽  
Tumour Necrosis ◽  
Community Acquired Pneumonia ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Factor Alpha ◽  
Kinetics Of ◽  
Lal Assay ◽  
Necrosis Factor

Former studies of our group have shown that the innate and adaptiveimmune status may differ in relation with the causative infection. To this sameend, it was investigated if kinetics of circulating lipopolysaccharide (LPS)leading to inflammatory response may differ. Blood was sampled from 189patients with sepsis and 206 with severe sepsis/shock starting 24 hours fromadvent of sepsis and repeating on day 3. Serum LPS was measured byLimulus Amebocyte Lysate (LAL) assay. From 59 patients, circulatingmonocytes were isolated and incubated in the absence/presence of LPS.Concentrations of tumour necrosis factor alpha (TNFα) were measured insupernatants by an enzyme immunoassay. In either category of severity,circulating LPS was greater among sufferers from primary Gram-negativebacteraemia (BSI) and from community-acquired pneumonia (CAP) thansufferers from other underlying infections. LPS were greater among patientswith BSI compared to patients with secondary Gram negative bacteraemia and patients without bacteraemia. Greater decrease of circulating LPS over48 hours was recorded for survivors compared to non survivors only withinsufferers from BSI and CAP. Significant endotoxemia was considered forpatients with serum LPS within the upper quartile of distribution; theirmonocytes were less potent for release of TNFα. It is concluded thatendotoxemia in sepsis varies greatly with the underlying infection; this isrelated with immunoparalysis of monocytes with implications on final outcome.

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