Antibiotics regulate the immune response in both presence and absence of lipopolysaccharide through modulation of Toll-like receptors, cytokine production and phagocytosis in vitro

The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As...

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Published inInternational immunopharmacology Vol. 18; no. 1; pp. 27 - 34
Main Authors Bode, Christian, Diedrich, Britta, Muenster, Stefan, Hentschel, Viktoria, Weisheit, Christina, Rommelsheim, Kuno, Hoeft, Andreas, Meyer, Rainer, Boehm, Olaf, Knuefermann, Pascal, Baumgarten, Georg
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Published Netherlands Elsevier B.V 01.01.2014
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Abstract The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1β, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis. •Antibiotics regulate the TLR- and cytokine expression in an in vitro sepsis model.•These effects are observed in PBMCs from patients with systemic inflammation.•Phagocytic activity of LPS-activated monocytes can be reduced by antibiotics.•Antibiotics differ in their ability to modulate TLR-and cytokine expression.•Moxifloxacin, doxycycline and erythromycin show the strongest modulation effects.
AbstractList The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1β, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis.
The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1β, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis. •Antibiotics regulate the TLR- and cytokine expression in an in vitro sepsis model.•These effects are observed in PBMCs from patients with systemic inflammation.•Phagocytic activity of LPS-activated monocytes can be reduced by antibiotics.•Antibiotics differ in their ability to modulate TLR-and cytokine expression.•Moxifloxacin, doxycycline and erythromycin show the strongest modulation effects.
The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24 h, mRNA levels of both cytokines (IL-1 beta , IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis.
Author Diedrich, Britta
Baumgarten, Georg
Muenster, Stefan
Hentschel, Viktoria
Rommelsheim, Kuno
Meyer, Rainer
Bode, Christian
Hoeft, Andreas
Weisheit, Christina
Boehm, Olaf
Knuefermann, Pascal
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– sequence: 2
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  surname: Muenster
  fullname: Muenster, Stefan
  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
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  givenname: Viktoria
  surname: Hentschel
  fullname: Hentschel, Viktoria
  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
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  givenname: Christina
  surname: Weisheit
  fullname: Weisheit, Christina
  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
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  fullname: Rommelsheim, Kuno
  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
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  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
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  surname: Meyer
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  organization: Institute of Physiology II, University of Bonn, Bonn, Germany
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  fullname: Knuefermann, Pascal
  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
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  givenname: Georg
  surname: Baumgarten
  fullname: Baumgarten, Georg
  organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24239744$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Toll-like receptors
Sepsis
Antibiotics
Cytokines
Immunomodulation
Phagocytosis
Language English
License http://creativecommons.org/licenses/by-nc-nd/3.0
Copyright © 2013. Published by Elsevier B.V.
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Snippet The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs)....
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SubjectTerms Anti-Bacterial Agents - pharmacology
Antibiotics
Cell Line
Cytokines
Cytokines - metabolism
Escherichia coli
Escherichia coli - metabolism
Escherichia coli Infections - drug therapy
Escherichia coli Infections - immunology
Gene Expression Regulation - drug effects
Humans
Immunomodulation
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - immunology
Lipopolysaccharides - immunology
Monocytes - drug effects
Monocytes - immunology
Phagocytosis
Phagocytosis - drug effects
Sepsis
Sepsis - drug therapy
Sepsis - immunology
Toll-like receptors
Toll-Like Receptors - drug effects
Toll-Like Receptors - immunology
Title Antibiotics regulate the immune response in both presence and absence of lipopolysaccharide through modulation of Toll-like receptors, cytokine production and phagocytosis in vitro
URI https://dx.doi.org/10.1016/j.intimp.2013.10.025
https://www.ncbi.nlm.nih.gov/pubmed/24239744
https://search.proquest.com/docview/1490743080
https://search.proquest.com/docview/1516739456
Volume 18
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