Linezolid, vancomycin and daptomycin modulate cytokine production, Toll-like receptors and phagocytosis in a human in vitro model of sepsis.
Conventional antibiotics exhibit immunomodulatory properties beneficial in the treatment of sepsis. Antibiotic-resistant Gram-positive bacteria have become a problem in sepsis therapy, giving rise to increased use of last-resort antibiotics; for example, linezolid (LIN), vancomycin (VAN) and daptomycin (DAP). As the immunomodulatory properties of these antibiotics in treating sepsis are unknown, this study examined the effect of VAN, LIN and DAP on the immune response under sepsis-like conditions in vitro. Lipopolysaccharide (LPS)-activated THP-1 monocytes were incubated with LIN, VAN or DAP. Gene expression of cytokines (TNFα, IL-1β, IL-6, IL-10) and Toll-like receptors (TLR1, 2, 4, 6, 7 and 9) was monitored and phagocytosis was determined following coincubation with E. coli. The antibiotics differentially modulated the gene expression of the investigated cytokines. While LIN and VAN upregulated the expression of all TLRs, DAP downregulated mRNA levels of TLR1, TLR2 and TLR6, which recognize pathogen-associated molecular patterns from Gram-positive bacteria. In addition, LIN inhibited, whereas VAN promoted the phagocytic activity of monocytes. Our results suggest that LIN and VAN possess pro-inflammatory properties, whereas DAP might reduce the immune response to Gram-positive bacteria in sepsis. Furthermore, VAN might be beneficial in the prevention of Gram-negative infections by increasing the phagocytosis of E. coli.
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Christian
C
Bode
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Stefan
S
Muenster
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.|Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
Britta
B
Diedrich
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Sebastian
S
Jahnert
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Christina
C
Weisheit
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Folkert
F
Steinhagen
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Olaf
O
Boehm
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Andreas
A
Hoeft
Institute of Physiology II, University of Bonn, Bonn, Germany.
Rainer
R
Meyer
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Georg
G
Baumgarten
D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D017576:Daptomycin / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D020869:Gene Expression Profiling; D006094:Gram-Positive Bacteria / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D000069349:Linezolid; D008962:Models, Theoretical; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D023303:Oxazolidinones / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D018805:Sepsis / Q000276:immunology*; D051193:Toll-Like Receptors / Q000096:biosynthesis*; D014640:Vancomycin / Q000494:pharmacology
D000081:Acetamides; D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D023303:Oxazolidinones; D051193:Toll-Like Receptors; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin