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Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model

INTRODUCTION: Sepsis is the primary cause of death from infection. We wanted to improve the outcome of sepsis by stimulating innate immunity in combination with modulating the severity of inflammatory responses in rats. METHOD: Sepsis was induced by the injection of feces suspension (control). A 5-d...

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Autores principales: Fang, Haoshu, Hua, Chuanfeng, Weiss, Stefanie, Liu, Anding, Cheng, Wenhui, Claus, Ralf, Rödel, Jürgen, Dirsch, Olaf, Dahmen, Uta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247567/
https://www.ncbi.nlm.nih.gov/pubmed/30525057
http://dx.doi.org/10.1155/2018/6085095
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author Fang, Haoshu
Hua, Chuanfeng
Weiss, Stefanie
Liu, Anding
Cheng, Wenhui
Claus, Ralf
Rödel, Jürgen
Dirsch, Olaf
Dahmen, Uta
author_facet Fang, Haoshu
Hua, Chuanfeng
Weiss, Stefanie
Liu, Anding
Cheng, Wenhui
Claus, Ralf
Rödel, Jürgen
Dirsch, Olaf
Dahmen, Uta
author_sort Fang, Haoshu
collection PubMed
description INTRODUCTION: Sepsis is the primary cause of death from infection. We wanted to improve the outcome of sepsis by stimulating innate immunity in combination with modulating the severity of inflammatory responses in rats. METHOD: Sepsis was induced by the injection of feces suspension (control). A 5-day course of G-CSF treatment was given before the septic insult (G-CSF). The inflammatory response was decreased using various doses of the LPS-blocking peptide LBPK95A (5 mg/kg = 100% Combi group, 0.5 mg/kg = 10% Combi group, and 0.05 mg/kg = 1% Combi group). Survival rates were observed. Bacterial clearance, neutrophil infiltration, tissue damage, and the induction of hepatic and systemic inflammatory responses were determined 2 h and 12 h after the septic insult. RESULTS: High-dose LBPK95A (100% Combi) reduced the survival rate to 10%, whereas low-dose LBPK95A (10% and 1% Combi) increased the survival rates to 50% and 80%, respectively. The survival rates inversely correlated with multiorgan damage as indicated by the serum levels of ALT and urea. G-CSF treatment increased the white blood cell counts, hepatic neutrophil infiltration, and bacterial clearance in the liver, lung, and blood. The blockade of the LPS-LBP interaction decreased neutrophil infiltration, led to increased white blood cell count, and decreased hepatic neutrophil infiltration, irrespective of dose. However, bacterial clearance improved in the 1% and 10% Combi groups but worsened in the 100% Combi group. G-CSF increased TNF-α and IL-6 levels. Irrespective of dose, the blockade of the LPS-LBP interaction was associated with low systemic cytokine levels and delayed increases in hepatic TNF-α and IL-6 mRNA expression. The delayed increase in cytokines was associated with the phosphorylation of STAT3 and AKT. CONCLUSION: Our results revealed that increasing innate immunity by G-CSF pretreatment and decreasing inflammatory responses using LBPK95A improved the survival rates in a rat sepsis model and could be a novel strategy to treat sepsis.
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spelling pubmed-62475672018-12-06 Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model Fang, Haoshu Hua, Chuanfeng Weiss, Stefanie Liu, Anding Cheng, Wenhui Claus, Ralf Rödel, Jürgen Dirsch, Olaf Dahmen, Uta J Immunol Res Research Article INTRODUCTION: Sepsis is the primary cause of death from infection. We wanted to improve the outcome of sepsis by stimulating innate immunity in combination with modulating the severity of inflammatory responses in rats. METHOD: Sepsis was induced by the injection of feces suspension (control). A 5-day course of G-CSF treatment was given before the septic insult (G-CSF). The inflammatory response was decreased using various doses of the LPS-blocking peptide LBPK95A (5 mg/kg = 100% Combi group, 0.5 mg/kg = 10% Combi group, and 0.05 mg/kg = 1% Combi group). Survival rates were observed. Bacterial clearance, neutrophil infiltration, tissue damage, and the induction of hepatic and systemic inflammatory responses were determined 2 h and 12 h after the septic insult. RESULTS: High-dose LBPK95A (100% Combi) reduced the survival rate to 10%, whereas low-dose LBPK95A (10% and 1% Combi) increased the survival rates to 50% and 80%, respectively. The survival rates inversely correlated with multiorgan damage as indicated by the serum levels of ALT and urea. G-CSF treatment increased the white blood cell counts, hepatic neutrophil infiltration, and bacterial clearance in the liver, lung, and blood. The blockade of the LPS-LBP interaction decreased neutrophil infiltration, led to increased white blood cell count, and decreased hepatic neutrophil infiltration, irrespective of dose. However, bacterial clearance improved in the 1% and 10% Combi groups but worsened in the 100% Combi group. G-CSF increased TNF-α and IL-6 levels. Irrespective of dose, the blockade of the LPS-LBP interaction was associated with low systemic cytokine levels and delayed increases in hepatic TNF-α and IL-6 mRNA expression. The delayed increase in cytokines was associated with the phosphorylation of STAT3 and AKT. CONCLUSION: Our results revealed that increasing innate immunity by G-CSF pretreatment and decreasing inflammatory responses using LBPK95A improved the survival rates in a rat sepsis model and could be a novel strategy to treat sepsis. Hindawi 2018-11-07 /pmc/articles/PMC6247567/ /pubmed/30525057 http://dx.doi.org/10.1155/2018/6085095 Text en Copyright © 2018 Haoshu Fang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Fang, Haoshu
Hua, Chuanfeng
Weiss, Stefanie
Liu, Anding
Cheng, Wenhui
Claus, Ralf
Rödel, Jürgen
Dirsch, Olaf
Dahmen, Uta
Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model
title Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model
title_full Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model
title_fullStr Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model
title_full_unstemmed Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model
title_short Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model
title_sort modulation of innate immunity by g-csf and inflammatory response by lbpk95a improves the outcome of sepsis in a rat model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247567/
https://www.ncbi.nlm.nih.gov/pubmed/30525057
http://dx.doi.org/10.1155/2018/6085095
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