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Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis

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Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis. / Mees, Soeren Torge; Toellner, Sietje; Marx, Kerstin; Faendrich, Fred; Kallen, Karl Josef; Schroeder, Joerg; Haier, Joerg; Kahlke, Volker.

in: J SURG RES, Jahrgang 157, Nr. 2, 12.2009, S. 235-42.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Mees, ST, Toellner, S, Marx, K, Faendrich, F, Kallen, KJ, Schroeder, J, Haier, J & Kahlke, V 2009, 'Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis', J SURG RES, Jg. 157, Nr. 2, S. 235-42. https://doi.org/10.1016/j.jss.2008.08.035

APA

Mees, S. T., Toellner, S., Marx, K., Faendrich, F., Kallen, K. J., Schroeder, J., Haier, J., & Kahlke, V. (2009). Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis. J SURG RES, 157(2), 235-42. https://doi.org/10.1016/j.jss.2008.08.035

Vancouver

Mees ST, Toellner S, Marx K, Faendrich F, Kallen KJ, Schroeder J et al. Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis. J SURG RES. 2009 Dez;157(2):235-42. https://doi.org/10.1016/j.jss.2008.08.035

Bibtex

@article{87d9433a00914fcb97dd96e3d13f9b17,
title = "Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis",
abstract = "BACKGROUND: Immune function after hemorrhagic shock and subsequent sepsis is characterized by an early proinflammatory burst of IL-6, and high IL-6 levels have been linked to high mortality after trauma and in sepsis. Trans-signaling is defined as the activation of cells that do not express the membrane bound IL-6 receptor by the complex of IL-6 and the soluble IL-6 receptor (sIL-6R). Gp130-Fc is able to bind the IL-6/sIL-6R complex, and beneficial effects of IL-6 blockade in chronic inflammatory diseases have been shown. The first aim of this study was to investigate the potential effect of a gp130 blockade via the gp130-Fc antibody causing impairment of IL-6 signaling. The second aim was to find out what role the IL-6/sIL-6R complex can play in the context of hemorrhagic shock and subsequent sepsis as an acute inflammatory disease.MATERIAL AND METHODS: Male CBA/J mice were subjected to hemorrhagic shock (35+/-5 mmHg for 90min and fluid resuscitation) or sham operation. At resuscitation each animal received either 0.5mg gp130-Fc or placebo (PL) i.p. At 48 h after resuscitation, both splenocytes and peritoneal macrophages (pMphi) were harvested or polymicrobial sepsis was induced by cecal ligation and puncture. Survival over 10 d was determined. Release of IL-6, TNF-alpha, and IL-10 of pMphi and release of IL-2, IL-10, and IFN-gamma of splenocytes was assessed by ELISA. Proliferation of splenocytes and their morphologic damage were determined.RESULTS: Binding of the IL-6/sIL-6R complex by gp130-Fc led to significant lower IL-6 levels compared with placebo treated animals. Placebo treated males showed depressed proinflammatory immune response (IL-2, IL-6) after hemorrhagic shock. While splenocyte proliferation was significantly reduced directly after hemorrhagic shock and restored after 48 h by gp130-Fc, pMphi cytokine release was not influenced. Finally, survival appeared to be unaffected.CONCLUSION: Transsignaling does not seem to play a pivotal role in the development of the immune dysfunction and mortality in our model of hemorrhage and subsequent sepsis.",
keywords = "Animals, Antibodies, Cell Proliferation, Cells, Cultured, Cytokine Receptor gp130, Disease Models, Animal, Ileum, Immune System, Interleukin-6, Kidney, Liver, Lung, Macrophages, Peritoneal, Male, Mice, Mice, Inbred CBA, Monokines, Receptors, Interleukin-6, Sepsis, Shock, Hemorrhagic, Signal Transduction, Spleen",
author = "Mees, {Soeren Torge} and Sietje Toellner and Kerstin Marx and Fred Faendrich and Kallen, {Karl Josef} and Joerg Schroeder and Joerg Haier and Volker Kahlke",
year = "2009",
month = dec,
doi = "10.1016/j.jss.2008.08.035",
language = "English",
volume = "157",
pages = "235--42",
journal = "J SURG RES",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis

AU - Mees, Soeren Torge

AU - Toellner, Sietje

AU - Marx, Kerstin

AU - Faendrich, Fred

AU - Kallen, Karl Josef

AU - Schroeder, Joerg

AU - Haier, Joerg

AU - Kahlke, Volker

PY - 2009/12

Y1 - 2009/12

N2 - BACKGROUND: Immune function after hemorrhagic shock and subsequent sepsis is characterized by an early proinflammatory burst of IL-6, and high IL-6 levels have been linked to high mortality after trauma and in sepsis. Trans-signaling is defined as the activation of cells that do not express the membrane bound IL-6 receptor by the complex of IL-6 and the soluble IL-6 receptor (sIL-6R). Gp130-Fc is able to bind the IL-6/sIL-6R complex, and beneficial effects of IL-6 blockade in chronic inflammatory diseases have been shown. The first aim of this study was to investigate the potential effect of a gp130 blockade via the gp130-Fc antibody causing impairment of IL-6 signaling. The second aim was to find out what role the IL-6/sIL-6R complex can play in the context of hemorrhagic shock and subsequent sepsis as an acute inflammatory disease.MATERIAL AND METHODS: Male CBA/J mice were subjected to hemorrhagic shock (35+/-5 mmHg for 90min and fluid resuscitation) or sham operation. At resuscitation each animal received either 0.5mg gp130-Fc or placebo (PL) i.p. At 48 h after resuscitation, both splenocytes and peritoneal macrophages (pMphi) were harvested or polymicrobial sepsis was induced by cecal ligation and puncture. Survival over 10 d was determined. Release of IL-6, TNF-alpha, and IL-10 of pMphi and release of IL-2, IL-10, and IFN-gamma of splenocytes was assessed by ELISA. Proliferation of splenocytes and their morphologic damage were determined.RESULTS: Binding of the IL-6/sIL-6R complex by gp130-Fc led to significant lower IL-6 levels compared with placebo treated animals. Placebo treated males showed depressed proinflammatory immune response (IL-2, IL-6) after hemorrhagic shock. While splenocyte proliferation was significantly reduced directly after hemorrhagic shock and restored after 48 h by gp130-Fc, pMphi cytokine release was not influenced. Finally, survival appeared to be unaffected.CONCLUSION: Transsignaling does not seem to play a pivotal role in the development of the immune dysfunction and mortality in our model of hemorrhage and subsequent sepsis.

AB - BACKGROUND: Immune function after hemorrhagic shock and subsequent sepsis is characterized by an early proinflammatory burst of IL-6, and high IL-6 levels have been linked to high mortality after trauma and in sepsis. Trans-signaling is defined as the activation of cells that do not express the membrane bound IL-6 receptor by the complex of IL-6 and the soluble IL-6 receptor (sIL-6R). Gp130-Fc is able to bind the IL-6/sIL-6R complex, and beneficial effects of IL-6 blockade in chronic inflammatory diseases have been shown. The first aim of this study was to investigate the potential effect of a gp130 blockade via the gp130-Fc antibody causing impairment of IL-6 signaling. The second aim was to find out what role the IL-6/sIL-6R complex can play in the context of hemorrhagic shock and subsequent sepsis as an acute inflammatory disease.MATERIAL AND METHODS: Male CBA/J mice were subjected to hemorrhagic shock (35+/-5 mmHg for 90min and fluid resuscitation) or sham operation. At resuscitation each animal received either 0.5mg gp130-Fc or placebo (PL) i.p. At 48 h after resuscitation, both splenocytes and peritoneal macrophages (pMphi) were harvested or polymicrobial sepsis was induced by cecal ligation and puncture. Survival over 10 d was determined. Release of IL-6, TNF-alpha, and IL-10 of pMphi and release of IL-2, IL-10, and IFN-gamma of splenocytes was assessed by ELISA. Proliferation of splenocytes and their morphologic damage were determined.RESULTS: Binding of the IL-6/sIL-6R complex by gp130-Fc led to significant lower IL-6 levels compared with placebo treated animals. Placebo treated males showed depressed proinflammatory immune response (IL-2, IL-6) after hemorrhagic shock. While splenocyte proliferation was significantly reduced directly after hemorrhagic shock and restored after 48 h by gp130-Fc, pMphi cytokine release was not influenced. Finally, survival appeared to be unaffected.CONCLUSION: Transsignaling does not seem to play a pivotal role in the development of the immune dysfunction and mortality in our model of hemorrhage and subsequent sepsis.

KW - Animals

KW - Antibodies

KW - Cell Proliferation

KW - Cells, Cultured

KW - Cytokine Receptor gp130

KW - Disease Models, Animal

KW - Ileum

KW - Immune System

KW - Interleukin-6

KW - Kidney

KW - Liver

KW - Lung

KW - Macrophages, Peritoneal

KW - Male

KW - Mice

KW - Mice, Inbred CBA

KW - Monokines

KW - Receptors, Interleukin-6

KW - Sepsis

KW - Shock, Hemorrhagic

KW - Signal Transduction

KW - Spleen

U2 - 10.1016/j.jss.2008.08.035

DO - 10.1016/j.jss.2008.08.035

M3 - SCORING: Journal article

C2 - 19589542

VL - 157

SP - 235

EP - 242

JO - J SURG RES

JF - J SURG RES

SN - 0022-4804

IS - 2

ER -