Interleukin 1 and Its Relationship to Endotoxin Tolerance

León, P Betancor; Redmond, H. P.; Shou, Jian; Daly, J.M.

doi:10.1001/archsurg.1992.01420020028004

Cited by 39 publications

(19 citation statements)

References 37 publications

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“…Although other cytokines, such as IL-10 [9], TGF-b [9], IL-13 [8] and IL-1a [13], have also been involved in the mechanism of refractoriness to LPS, our results are probably only a partial expression of the complex phenomenon of endotoxin tolerance. However, we think that the study of mechanisms of IL-1b-induced tolerance leading to an anti-inflammatory activity deserve further investigation in the future.…”

Section: Discussionmentioning

confidence: 72%

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Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

Alves-Rosa

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Beigier-Bompadre

et al. 2002

Clinical and Experimental Immunology

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SUMMARYEndotoxin or lipopolysaccharide (LPS) tolerance may be partially due to the secretion of potent antiinflammatory cytokines following severe Gram-negative infections, or by low doses of LPS. In this work, we describe the effects of interleukin-1b (IL-1b) and tumour necrosis factor alpha (TNF-a), two early cytokines secreted after LPS exposure, in the induction of LPS tolerance. Our results demonstrate that mice treated with three daily doses of 100 ng of IL-1b were tolerant to LPS-induced shock. However, TNF-a was unable to induce an LPS refractory state. Given the fact that 100 ng of IL-1b increase the plasma levels of glucocorticoids, we evaluated whether a daily injection of dexamethasone (DEX) alone was able to reproduce the LPS-like tolerant state. However, no signs of LPS refractoriness were detected, except when DEX was administered concomitantly with a dose of IL-1b that does not induce corticosterone secretion (12 ng/mouse). This dose was found to induce in vitro up-regulation of the glucocorticoid receptors (GcR) of peritoneal macrophages following 24 h of treatment. In addition, we demonstrate that IL-1b is capable of inducing the down-regulation of Toll-like receptor 4 (TLR4), a crucial molecule in the signal transduction of LPS. Taken together, our results indicate that IL-1b can generate tolerance to LPS in vivo, and suggest that the regulation of mechanisms of the downregulation of TLR4, as well as those involved in the expression of GcR and/or in the secretion of glucocorticoids, would be crucial for these effects.

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Section: Discussionmentioning

confidence: 72%

“…Endotoxin desensitization has also been achieved in vitro with relative efficacy by individual cytokines, such as IL-10 [9] and transforming growth factor-b (TGF-b) [9], and in vivo by injection of IL-13 [8] and IL-1a [13].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

Alves-Rosa

Vulcano

Beigier-Bompadre

et al. 2002

Clinical and Experimental Immunology

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“…In this study, TNF-α expression remained elevated; therefore, a different mechanism for ET induction was suspected than in ET associated with low TNF-α expression (Leon et al 1992). …”

Section: Il-1mentioning

confidence: 63%

“…Potentially beneficial effects of IL-6 production during endotoxemia have been described and include decreased production of TNF-α and IL-6 by monocytes, and inducing production of the full range of acute-phase proteins, including protease inhibitors that are postulated to limit tissue damage (Robinson et al 1993). Other studies, however, have indicated that IL-6 may contribute to the pathogenic effects of gram negative infections or intravenous administration of TNF-α and that administration of IL-6 antagonists may be beneficial in endotoxemia (Leon et al 1992;Starnes et al 1990). LPS infusion in neonatal foals led to an increased production of IL-6 (Robinson et al 1993).…”

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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“…IL-1a appears in serum later than does TNFa, and is detectable after 1 hr, reaching its maximum levels between 2 and 3 hr [10]. IL-6 increases progressively and continuously, reaching its maximum value after 4 hr [11,12] (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%