Journal Article

Vancomycin and daptomycin modulate the innate immune response in a murine model of LPS-induced sepsis

Baumgarten, Georg, Muenster, Stefan, Coburn, Mark, Zschernack, Valentina, Dierig, Birte, Frede, Stilla, Putensen, Christian, Weisheit, Christina Katharina

2021

Overview

Sepsis is a leading cause of death worldwide, despite the use of multimodal therapies. Common antibiotic regimens are being affected by a rising number of multidrug-resistant pathogens, and new therapeutic approaches are therefore needed. Antibiotics have immunomodulatory properties which appear to be beneficial in the treatment of sepsis. We hypothesized that the last-resort antibiotics vancomycin (VAN) and daptomycin (DMC) modulate cell migration, phagocytosis, and protein cytokine levels in a murine model of lipopolysaccharide (LPS)-induced sepsis. Ten to twelve-week-old C57BL/6 mice (n = 4–6 animals per group) were stimulated with LPS for 20 h, followed by the administration of VAN or DMC. The outcome parameters were leukocyte accumulation and effector function. Quantification of the immune cells in the peritoneal lavage was performed using flow cytometry analysis. Phagocytosis was measured using pHrodo E. coli BioParticles. The response of the cytokines TNFα, IL-6, and IL-10 was measured in vitro using murine peritoneal macrophages stimulated with LPS and VAN or DMC. VAN decreased both the peritoneal macrophage and the dendritic cell populations following LPS stimulation. DMC reduced the dendritic cell population in the peritoneal cavity in LPS-infected mice. Both antibiotics increased the phagocytic activity in peritoneal macrophages, but this effect was diminished in response to LPS. Phagocytosis of dendritic cells was increased in LPS-infected animals treated with VAN. VAN and DMC differently modulated the levels of pro-and anti-inflammatory cytokines. In a murine model of LPS-induced sepsis, VAN and DMC exhibit immunomodulatory effects on cells involved in innate immunity. The question of whether these antibiotics exhibit synergistic effects in the treatment of septic patients, beyond their bactericidal properties, should be further evaluated in future studies.

• Publisher: SAGE Publications,Sage Publications Ltd
• Subject: Animal models / Animals / Anti-Bacterial Agents - pharmacology / Antibiotics / Cytokines / Cytokines - metabolism / Daptomycin / Daptomycin - pharmacology / Dendritic cells / Dendritic Cells - drug effects / Flow cytometry / Immune response / Immunity, Innate - drug effects / Immunomodulation / Immunomodulators / Inflammation / Innate immunity / Interleukin 10 / Interleukin 6 / Leukocyte Count / Leukocyte migration / Lipopolysaccharides / Macrophages / Macrophages, Peritoneal - drug effects / Male / Mice / Mice, Inbred C57BL / Multidrug resistance / Original / Peritoneal Cavity - cytology / Peritoneum / Phagocytes / Phagocytosis / Phagocytosis - drug effects / Sepsis / Sepsis - chemically induced / Sepsis - immunology / Tumor necrosis factor-α / Vancomycin / Vancomycin - pharmacology