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Low-dose polymyxin: an option for therapy of Gram-negative sepsis.

Harm S, Gabor F, Hartmann J - Innate Immun (2016)

Bottom Line: The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion.Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model.Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.

View Article: PubMed Central - PubMed

Affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.

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Related in: MedlinePlus

The effect of LPS inactivation by PMB on cytokine release in whole blood from three different donors (mean ± SD; n = 3).
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fig5-1753425916639120: The effect of LPS inactivation by PMB on cytokine release in whole blood from three different donors (mean ± SD; n = 3).

Mentions: Although the LAL test revealed inactivation of LPS by PMB in a concentration-dependent manner, the influence on inflammation was tested by stimulating leukocytes from human blood with increasing amounts of PMB. The results of cytokine release show clearly that the formed LPS–PMB complex exerts a by far lower stimulating effect on blood cells than the native LPS molecule (Table 1; Figure 5). Among all cytokines under investigation, the highest impact was observed on TNF-α release. Only 50 ng PMB per ml blood reduced TNF-α secretion from leukocytes by 87.4 ± 5.9%. Increasing the PMB 2.5-fold to 125 ng/ml decreased the TNF-α level by about 94.8 ± 2.3%. A further increase of PMB caused no considerable decrease of cytokine concentrations (Table 1). The lowest impact of PMB was observed on IL-8 secretion. However, even the negative control without LPS showed high levels of IL-8. In general, the IL-10 level was very low (23 ± 8 pg/ml) because IL-10 is a late-related cytokine and a high level can only be reached if stimulation of the blood cells is prolonged to 12 h. The secretion of IL-1β was reduced by 75.1 ± 10.8% and that of IL-6 by 78.0 ± 12.0% in the presence of 125 ng PMB per ml blood.Figure 5.


Low-dose polymyxin: an option for therapy of Gram-negative sepsis.

Harm S, Gabor F, Hartmann J - Innate Immun (2016)

The effect of LPS inactivation by PMB on cytokine release in whole blood from three different donors (mean ± SD; n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4834512&req=5

fig5-1753425916639120: The effect of LPS inactivation by PMB on cytokine release in whole blood from three different donors (mean ± SD; n = 3).
Mentions: Although the LAL test revealed inactivation of LPS by PMB in a concentration-dependent manner, the influence on inflammation was tested by stimulating leukocytes from human blood with increasing amounts of PMB. The results of cytokine release show clearly that the formed LPS–PMB complex exerts a by far lower stimulating effect on blood cells than the native LPS molecule (Table 1; Figure 5). Among all cytokines under investigation, the highest impact was observed on TNF-α release. Only 50 ng PMB per ml blood reduced TNF-α secretion from leukocytes by 87.4 ± 5.9%. Increasing the PMB 2.5-fold to 125 ng/ml decreased the TNF-α level by about 94.8 ± 2.3%. A further increase of PMB caused no considerable decrease of cytokine concentrations (Table 1). The lowest impact of PMB was observed on IL-8 secretion. However, even the negative control without LPS showed high levels of IL-8. In general, the IL-10 level was very low (23 ± 8 pg/ml) because IL-10 is a late-related cytokine and a high level can only be reached if stimulation of the blood cells is prolonged to 12 h. The secretion of IL-1β was reduced by 75.1 ± 10.8% and that of IL-6 by 78.0 ± 12.0% in the presence of 125 ng PMB per ml blood.Figure 5.

Bottom Line: The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion.Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model.Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.

View Article: PubMed Central - PubMed

Affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.

No MeSH data available.


Related in: MedlinePlus