Tumor necrosis factor alpha and interleukin 6 release induced by antibiotic killing ofPseudomonas aeruginosa andStaphylococcus aureus

Schneider, Christian; Huzly, Daniela; Vetter, C.; Specht, B U von; Daschner, Franz

doi:10.1007/bf02471914

Cited by 10 publications

(5 citation statements)

References 12 publications

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“…26 It is also possible that antibiotics, particularly those used in cystic fibrosis, could be responsible for upregulation of cytokine production, 27 and that ceftazidime in the presence of organisms can lead to higher concentrations of IL-6 and TNF-a than other antibiotics. 28,29 This upregulation of cytokines by antibiotics, associated with endotoxin-induced cytokine release from bacterial killing, might mask any potential benefit to measured sputum cytokines afforded by courses of IV antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis

Cunningham

McColm

Mallinson

et al. 2003

Pediatric Pulmonology

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Intravenous (IV) antibiotics are a mainstay of therapy in children with cystic fibrosis. It is unclear, however, over what period associated improvements in pulmonary function are maintained, and to what extent the underlying inflammatory process is impeded in children admitted for a course of IV antibiotics. This was a prospective, interventional study of 14 children (median age, 14 years; interquartile range, 10-14) with cystic fibrosis who were regular sputum producers and who required admission for a 2-week course of IV antibiotics. Children performed spirometry and provided a sputum sample prior to starting IV antibiotics and then weekly for 6 weeks, the first 2 weeks of which IV antibiotics were given. Sputum IL-8, TNF-alpha, IL-6, IL-10, MIP1-alpha, and elastase were measured. Seven children were asked to repeat the protocol in a subsequent exacerbation to assess similarities in response to therapy. Significant improvements were seen in forced expired volume in 1 sec (FEV(1)) in association with IV antibiotics (27% relative improvement in predicted from baseline to end of week 1, median FEV(1) 41.3% increasing to 52.2%), but this continued only 1 week following cessation of antibiotics. Although IL-8 demonstrated a trend for reduction in association with antibiotics, no significant profile was demonstrated for any of the cytokines assessed. IL-10 was detectable in 64% of samples (all <100 pg/ml). In children with two episodes assessed, although there was a close correlation of FEV(1) and FVC between exacerbations (before antibiotics), no significant correlation was seen for IL-8, TNF-alpha, or IL-10 measured in both sets of samples at any sample point (indeed, a discordant response was seen between sample points in the two exacerbations). Although FEV(1) temporarily improves in response to admission for IV antibiotics, no such response is seen in sputum cytokine values. In addition, assessment of cytokines in subsequent exacerbations does not show a similar pattern of response to treatment.

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Section: Discussionmentioning

confidence: 99%

Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis

Cunningham

McColm

Mallinson

et al. 2003

Pediatric Pulmonology

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“…Ex vivo [40,41,67,69,71,72] and in vivo [20] studies of cytokine and chemokine response to bacteria or their components, in concert with antibiotic intervention, are of increasing interest, and inevitably, this should result in improved therapeutic intervention strategies, including those derived in part from corresponding studies of glucocorticoid efficacy.…”

Section: Tnf-␣ Release Linked To Antibiotic Chemotherapymentioning

confidence: 99%

Endogenous versus exogenous glucocorticoid responses to experimental bacterial sepsis

Silverstein

Johnson

2003

Journal of Leukocyte Biology

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Although lack of adrenals dramatically reduces resistance against sepsis generally, the value of glucocorticoid levels above those normally produced by stress remains controversial. An early and long-held concept is that glucocorticoid protection against lipopolysaccharides in animal models is important. Supporting this concept, C3H/HeJ mice, lacking Toll-like receptor-4 (TLR-4), and consequently, endotoxin hyporesponsive, have recently been shown to be resistant to glucocorticoid protection against live Escherichia coli. Effective antibiotic intervention, as an additional parameter and with concomitant administration of glucocorticoid, not only allows for expected antibiotic protection but also for glucocorticoid protection against E. coli or Staphylococcus aureus of mice sensitized to tumor necrosis factor alpha, regardless of the status of the TLR-4 receptor. TLRs, including but not limited to TLR-2, may be involved in glucocorticoid protective efficacy against Gram-positive and Gram-negative sepsis. Overlapping and possibly endotoxin-independent signaling may become important considerations.

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“…Nevertheless, there have been several earlier studies from our laboratory (3,17,24; D. C. Morrison, Editorial, J. Endotoxin Res. 3:171, 1996) and from other laboratories (8,11,(20)(21)(22)(29)(30)(31) establishing that killing or otherwise inhibiting proliferation of bacteria through the use of efficacious antibiotic treatments can significantly alter inflammatory responses depending on the bacteria and specific antibiotic(s). We therefore investigated the effect of one such antibiotic, imipenem, which effectively kills both gram-positive and gram-negative microbes in vivo and in vitro.…”

Section: Vol 68 2000 Macrophage Responses To Gram-positive and -Negmentioning

confidence: 99%

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

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Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-␣) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-␣ mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-␣ 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-␣ 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-␣ response. Both the magnitude and kinetic profile of the TNF-␣ 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-␣ response, with the appearance of an early TNF-␣ peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies ( . In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-␣ 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-␣ profiles faithfully reflect circulating levels of TNF-␣ in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-␣) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.

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Tumor necrosis factor alpha and interleukin 6 release induced by antibiotic killing ofPseudomonas aeruginosa andStaphylococcus aureus

Cited by 10 publications

References 12 publications

Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis

Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis

Endogenous versus exogenous glucocorticoid responses to experimental bacterial sepsis

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

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