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 in | International immunopharmacology Vol. 18; no. 1; pp. 27 - 34 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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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. |
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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 |
Author_xml | – sequence: 1 givenname: Christian surname: Bode fullname: Bode, Christian email: christian.bode@ukb.uni-bonn.de organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 2 givenname: Britta surname: Diedrich fullname: Diedrich, Britta organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 3 givenname: Stefan surname: Muenster fullname: Muenster, Stefan organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 4 givenname: Viktoria surname: Hentschel fullname: Hentschel, Viktoria organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 5 givenname: Christina surname: Weisheit fullname: Weisheit, Christina organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 6 givenname: Kuno surname: Rommelsheim fullname: Rommelsheim, Kuno organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 7 givenname: Andreas surname: Hoeft fullname: Hoeft, Andreas organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 8 givenname: Rainer surname: Meyer fullname: Meyer, Rainer organization: Institute of Physiology II, University of Bonn, Bonn, Germany – sequence: 9 givenname: Olaf surname: Boehm fullname: Boehm, Olaf organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 10 givenname: Pascal surname: Knuefermann fullname: Knuefermann, Pascal organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany – sequence: 11 givenname: Georg surname: Baumgarten fullname: Baumgarten, Georg organization: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany |
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Keywords | Toll-like receptors Sepsis Antibiotics Cytokines Immunomodulation Phagocytosis |
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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 |
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