Endotoxin, tumor necrosis factor-α and interleukin 1 induce interleukin 6 production in vivo

Shalaby, M. R.; Waage, Anders; Aarden, Lucien A.; Espevik, Terje

doi:10.1016/0090-1229(89)90010-x

Cited by 288 publications

(136 citation statements)

References 18 publications

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“…Next, we tested whether Pf3R and Pt1 treatments elicited different inflammatory responses. TNF-␣ is usually the first of the early cytokines found after the administration of endotoxin (11), whereas IL-6 levels increase later, as a direct response to elevated TNF-␣ levels (28). TNF-␣ and IL-6 levels in serum samples from two groups of mice inoculated with five times the MLD (5 ϫ 10 8 CFU) were determined before bacterial challenge, 60 min after bacterial challenge, and 2, 4, and 6 h after treatment with phage Pt1 or Pf3R.…”

Section: Resultsmentioning

confidence: 99%

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Hagens

Habel

Ahsen

et al. 2004

Antimicrob Agents Chemother

168

111

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Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which mediate the general pathological aspects of septicemia. Here we explored an alternative strategy by using genetically engineered nonreplicating, nonlytic phage to combat an experimental Pseudomonas aeruginosa infection. An export protein gene of the P. aeruginosa filamentous phage Pf3 was replaced with a restriction endonuclease gene. This rendered the Pf3 variant (Pf3R) nonreplicative and concomitantly prevented the release of the therapeutic agent from the target cell. The Pf3R phage efficiently killed a wild-type host in vitro, while endotoxin release was kept to a minimum. Treatment of P. aeruginosa infections of mice with Pf3R or with a replicating lytic phage resulted in comparable survival rates upon challenge with a minimal lethal dose of 3. However, the survival rate after phage therapy with Pf3R was significantly higher than that with the lytic phage upon challenge with a minimal lethal dose of 5. This higher survival rate correlated with a reduced inflammatory response elicited by Pf3R treatment relative to that with the lytic phage. Therefore, this study suggests that the increased survival rate of Pf3R-treated mice could result from reduced endotoxin release. Thus, the use of a nonreplicating modified phage for the delivery of genes encoding proteins toxic to bacterial pathogens may open up a new avenue in antimicrobial therapy.

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Section: Resultsmentioning

confidence: 99%

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Hagens

Habel

Ahsen

et al. 2004

Antimicrob Agents Chemother

168

111

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“…A number of studies have associated ethanol exposure with dramatic changes in the production of a number of cytokines including IL-1, transforming growth factor ␤, and TNF-␣ [41,42]. These potent cytokines are also known to be elevated after thermal injury and sepsis [8,11] and have been shown to increase circulating and cell-derived IL-6 [43][44][45]. Therefore, it is possible that the changes in IL-6 production observed here may be a result of modulation by other cytokines as well as mediators such as prostaglandins and oxygen free radicals.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6

Faunce

Gregory

Kovacs

1998

Journal of Leukocyte Biology

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Previous reports by this laboratory demonstrated that acute alcohol exposure combined with a 15% body surface area dorsal scald injury results in significant reductions in delayed-type hypersensitivity (DTH) and splenocyte proliferative responses compared to either insult alone. Previous studies by this lab have also shown that these defects are mediated, in part, by increased production of interleukin-6 (IL-6). Because both alcohol exposure and thermal injury are known to modulate glucocorticoid (CORT) levels, and CORT regulates IL-6 gene expression, the relationship between circulating CORT and IL-6 production in burn ؉ ethanol mice was examined . At 24 and 48 h post-burn, a positive correlation existed between circulating CORT levels and measurements of cellular immune function. Administration of exogenous CORT to burn ؉ ethanol-treated mice resulted in significant restoration (to 60% of control) of DTH and splenocyte proliferative responses. This restoration was concomitant with a down-regulation of circulating and macrophage-derived IL-6. The specificity of CORT in modulating these responses was tested by assessing cellular immune function and IL-6 levels after glucocorticoid receptor blockade with RU486. Taken together, these data strongly suggest that under normal circumstances CORT protects burned mice from severe immune dysfunction, a protection that is not afforded to burn ؉ ethanol-treated mice. Furthermore, the immune dysfunction observed in burn ؉ ethanol mice may be due to a lack of glucocorticoid attenuation of IL-6. J. Leukoc. Biol. 64: 724-732; 1998.

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“…The concentration of IL-6 in compartmentalized body fluids and in the circulation is high in animals with infectious, traumatic, autoimmune, and neoplastic diseases (Hirano 1992;Van Snick 1990). Gram negative bacterial endotoxin is a potent stimulus for IL-6 production, acting either directly (Fong et al 1989) or indirectly through induction of other cytokines, such as IL-1 and TNF-α (Fong et al 1989;Shalaby et al 1989).…”

Section: Il-6mentioning

confidence: 99%

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

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Endotoxemia is responsible for severe illness in horses. Individuals can become unresponsive to the endotoxin molecule after an initial exposure; this phenomenon has been called developing a state of 'endotoxin tolerance' (ET). ET has been induced in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMCs) in vitro, and to describe the cytokine profile which is associated with the ET.Blood was collected from 6 healthy horses and PBMCs were isolated. ET was induced by culturing cells with three concentrations of endotoxin given to induce ET, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR.ET was induced in all cells (n=6) exposed to the 2-step endotoxin challenge. In PBMCs treated with 1.0 ng/ml of endotoxin followed by challenge with 10 ng/ml of endotoxin, the relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge compared with positive control cells.This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMCs. A marked suppression of IL-12 production is associated with ET. The production of IL-10 was not altered in ET in our model.

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Endotoxin, tumor necrosis factor-α and interleukin 1 induce interleukin 6 production in vivo

Cited by 288 publications

References 18 publications

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

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