Inhibiting early activation of tissue nuclear factor-κB and nuclear factor interleukin 6 with (1→3)-β-D -glucan increases long-term survival in polymicrobial sepsis

Williams, David L.; Ha, Tuanzhu; Li, Chaunfu; Kalbfleisch, John H.; Laffan, John J.; Ferguson, Donald

doi:10.1067/msy.1999.99058

Cited by 77 publications

(91 citation statements)

References 44 publications

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“…Previous studies suggested that the beneficial effect of ketamine on survival was probably achieved by attenuating production of inflammatory cytokines (10, 33). Moreover, it was implied that inhibiting NF-κB activation and TLR2 and TLR4 expression correlated with survival improvement in sepsis (34,35). Therefore, we hypothesized that, in the CLP model of sepsis, ketamine might improve survival by suppressing production of inflammatory cytokines, NF-κB activation and TLR2 and TLR4 expression.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ketamine on Pulmonary Inflammatory Responses and Survival in Rats Exposed to Polymicrobial Sepsis

Shao

Yang

et al. 2007

J Pharm Pharm Sci

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-PURPOSE.Ketamine is reported to suppress production of proinflammatory cytokines and activity of nuclear factor-kappa B (NF-κB) after lipopolysaccharide (LPS) stimulation. Our study was designed to investigate the effects of ketamine on pulmonary inflammatory responses and survival in a clinically relevant model of polymicrobial sepsis, induced by cecal ligation and puncture (CLP). METHODS. After the induction of sepsis or sham-operation, animals were treated with ketamine (0.5, 5 or 10 mg/kg) or saline (10 ml/kg) at 3h after operation. At 6 h post-operation, the levels of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6, activity of NF-κB, expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of the lungs were measured. And the mortality was recorded for 7 days. RESULTS. TNF-α and IL-6 production, NF-κB activity, TLR2 and TLR4 expression in rat lungs were increased after CLP. Ketamine at the doses of 5 mg/kg and 10 mg/kg suppressed CLP-induced elevation of TNF-α and IL-6 production, NF-κB activity and TLR2 expression. Ketamine 0.5, 5 and 10 mg/kg inhibited TLR4 expression in sepsis. Ketamine 5mg/kg and 10 mg/kg after CLP improved the survival of rats. CONCLUSIONS. Ketamine at sub-anesthetic doses could suppress the production of inflammatory cytokines such as TNF-α and IL-6, attenuate NF-κB activity, and inhibit TLR2 and TLR4 expression in polymicrobial sepsis. These anti-inflammatory effects of ketamine may correlate with improved survival in sepsis.

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Section: Discussionmentioning

confidence: 99%

Effects of Ketamine on Pulmonary Inflammatory Responses and Survival in Rats Exposed to Polymicrobial Sepsis

Shao

Yang

et al. 2007

J Pharm Pharm Sci

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“…Despite this proinflammatory role, β-glucans may decrease tissue damage in already established inflammatory processes [11]. …”

Section: Introductionmentioning

confidence: 99%

Lentinula edodes β-glucan enriched diet induces pro- and anti-inflammatory macrophages in rabbit

Crespo

Guillén²,

Pablo-Maiso

et al. 2017

Food & Nutrition Research

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ABSTRACTβ-glucans exhibited in cell walls of several pathogens as bacteria or fungi are sensed by pathogen recognition receptors such as scavenger receptors present in antigen presenting cells, i.e., macrophages. β-glucans obtained from Shiitake mushrooms were chemically characterized. A β-glucan supplemented diet was assayed for 30 days in rabbits aiming to characterize the immune response elicited in blood-derived macrophages. M1 and M2 profiles of macrophage differentiation were confirmed in rabbits by in vitro stimulation with IFN-γ and IL-4 and marker quantification of each differentiation pathway. Blood derived macrophages from rabbits administered in vivo with the β-glucan supplemented diet showed higher IL-4, IFN-γ and RAGE together with lower IL-10 relative expression, indicative of an ongoing immune response. Differences in IL-1β, IL-13 and IL-4 expression were also found in rabbit sera by ELISA suggesting further stimulation of the adaptive response. Recent challenges in the rabbit industry include the search of diet supplements able to elicit an immune stimulation with particular interest in facing pathogens such as viruses or bacteria. β–glucans from fungi may contribute to maintain an immune steady state favouring protection and thus reducing antibiotic treatment.

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“…We have previously reported that the immunomodulator glucan phosphate (GP) induces protection in a murine model of cecal ligation and puncture (CLP)-induced polymicrobial sepsis and septic shock (9). We have been studying the cellular and molecular mechanisms associated with GP-induced protection in the CLP model (9,10).…”

mentioning

confidence: 99%

“…However, the role of the PI3K pathway in response to a clinically relevant model of sepsis and inflammation has not been studied. We investigated the effect of inhibiting PI3K activity in a murine model of polymicrobial sepsis (7)(8)(9). We focused on tissue PI3K activity, serum cytokine levels, splenocyte apoptosis, and survival outcome.…”

mentioning

confidence: 99%

Modulation of the Phosphoinositide 3-Kinase Pathway Alters Innate Resistance to Polymicrobial Sepsis

Williams¹,

Li²,

Ha³

et al. 2004

The Journal of Immunology

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154

162

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We examined the effect of modulating phosphoinositide 3-kinase (PI3K) activity in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Inhibition of PI3K activity with wortmannin increased serum cytokine levels and decreased survival time in septic mice. We have reported that an immunomodulator, glucan phosphate, induces protection in murine polymicrobial sepsis. We observed that glucan stimulated tissue PI3K activity, which positively correlated with increased survival in septic mice. We investigated the effect of PI3K inhibition on survival in septic mice treated with glucan. Treatment of mice with the PI3K inhibitors, wortmannin and LY294002, completely eliminated the protective effect of glucan, indicating that protection against septic mortality was mediated through PI3K. Inhibition of PI3K resulted in increased serum levels of IL1-β, IL-2, IL-6, IL-10, IL-12, and TNF-α in septic mice. Apoptosis is thought to play a central role in the response to septic injury. We observed that inhibition of PI3K activity in septic mice resulted in increased splenocyte apoptosis and a change in the anatomic distribution of splenocyte apoptosis. We conclude that PI3K is a compensatory mechanism that suppresses proinflammatory and apoptotic processes in response to sepsis and/or inflammatory injury. Thus, PI3K may play a pivotal role in the maintenance of homeostasis and the integrity of the immune response during sepsis. We also observed that glucan phosphate decreased septic morbidity and mortality through a PI3K-dependent mechanism. This suggests that stimulation of the PI3K pathway may be an effective approach for preventing or treating sepsis and/or septic shock.

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Inhibiting early activation of tissue nuclear factor-κB and nuclear factor interleukin 6 with (1→3)-β-D -glucan increases long-term survival in polymicrobial sepsis

Cited by 77 publications

References 44 publications

Effects of Ketamine on Pulmonary Inflammatory Responses and Survival in Rats Exposed to Polymicrobial Sepsis

Effects of Ketamine on Pulmonary Inflammatory Responses and Survival in Rats Exposed to Polymicrobial Sepsis

Lentinula edodes β-glucan enriched diet induces pro- and anti-inflammatory macrophages in rabbit

Modulation of the Phosphoinositide 3-Kinase Pathway Alters Innate Resistance to Polymicrobial Sepsis

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