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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.

No MeSH data available.


Related in: MedlinePlus

Comparison of the cytokine release pattern from blood cells after different ways of plasma pre-treatments: adsorbent combined with PMB (Ads/PMB); only adsorbent (Ads); only PMB (PMB); untreated plasma (+ control); native blood (− control).
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fig6-1753425916639120: Comparison of the cytokine release pattern from blood cells after different ways of plasma pre-treatments: adsorbent combined with PMB (Ads/PMB); only adsorbent (Ads); only PMB (PMB); untreated plasma (+ control); native blood (− control).

Mentions: As pre-existing cytokines cannot be reduced by PMB infusion and the inflammatory acting LPS cannot be removed from blood by adsorption techniques sufficiently, these two types of treatments were simulated in an in vitro model (see Figure 1). Plasma that contained inflammatory mediators like LPS and secreted cytokines was pre-treated with adsorbent or PMB or both. Then, the treated plasma samples were incubated with blood cells from the same donor for 4 h and the cytokine levels were determined. Untreated plasma containing the inflammatory mediators served as a positive control and native blood as a negative control. According to the results, the addition of PMB after LPS stimulation scarcely reduced the cytokine secretion compared with the untreated plasma. The cytokine levels, however, were still high because of the presence of cytokines like TNF-α that still act as stimulating agents. Interestingly, the adsorbent CG161c decreased the cytokine level in plasma considerably to 30 ± 9% (TNF-α), 6 ± 5% (IL-1β), 2 ± 2% (IL-6), 1 ± 1% (IL-8) and 9 ± 13% (IL-10) compared with the untreated positive control. The styrene-divinylbenzene based CG161c adsorbent has a particle size of 120 µm and pores with an average diameter of 15 nm. In earlier studies, we have shown that CG161c is very effective in removing cytokines from plasma.25,26 After incubation of the different plasma samples with blood cells only the combination of adsorbent with PMB exhibited cytokine levels similar to the negative control where no LPS was added (see Table 2 and Figure 6). Obviously, PMB inactivates LPS and reduces leukocyte stimulation. The results show high SDs of the cytokine level due to the fact that blood from different donors was used.Figure 6.


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

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

Comparison of the cytokine release pattern from blood cells after different ways of plasma pre-treatments: adsorbent combined with PMB (Ads/PMB); only adsorbent (Ads); only PMB (PMB); untreated plasma (+ control); native blood (− control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6-1753425916639120: Comparison of the cytokine release pattern from blood cells after different ways of plasma pre-treatments: adsorbent combined with PMB (Ads/PMB); only adsorbent (Ads); only PMB (PMB); untreated plasma (+ control); native blood (− control).
Mentions: As pre-existing cytokines cannot be reduced by PMB infusion and the inflammatory acting LPS cannot be removed from blood by adsorption techniques sufficiently, these two types of treatments were simulated in an in vitro model (see Figure 1). Plasma that contained inflammatory mediators like LPS and secreted cytokines was pre-treated with adsorbent or PMB or both. Then, the treated plasma samples were incubated with blood cells from the same donor for 4 h and the cytokine levels were determined. Untreated plasma containing the inflammatory mediators served as a positive control and native blood as a negative control. According to the results, the addition of PMB after LPS stimulation scarcely reduced the cytokine secretion compared with the untreated plasma. The cytokine levels, however, were still high because of the presence of cytokines like TNF-α that still act as stimulating agents. Interestingly, the adsorbent CG161c decreased the cytokine level in plasma considerably to 30 ± 9% (TNF-α), 6 ± 5% (IL-1β), 2 ± 2% (IL-6), 1 ± 1% (IL-8) and 9 ± 13% (IL-10) compared with the untreated positive control. The styrene-divinylbenzene based CG161c adsorbent has a particle size of 120 µm and pores with an average diameter of 15 nm. In earlier studies, we have shown that CG161c is very effective in removing cytokines from plasma.25,26 After incubation of the different plasma samples with blood cells only the combination of adsorbent with PMB exhibited cytokine levels similar to the negative control where no LPS was added (see Table 2 and Figure 6). Obviously, PMB inactivates LPS and reduces leukocyte stimulation. The results show high SDs of the cytokine level due to the fact that blood from different donors was used.Figure 6.

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