title: Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro model.
abstract: BACKGROUND
  Sepsis may lead to the suppression of stimulated cytokine release after Gram-negative stimuli, correlating with a fatal outcome. Treatment of sepsis includes adequate therapy with antibiotics. The aim of this study was to investigate the role of antibiotics in the modulation of the lipopolysaccharide (LPS)-stimulated cytokine response of human monocytes.
  
  
  METHODS
  In this ex vivo, in vitro study, whole blood samples were taken from 10 healthy volunteers, stimulated with LPS in the presence or absence of various antibiotics (penicillin, amoxicillin, cefuroxime, ceftazidime, cefotaxime, piperacillin/tazobactam, imipenem/cilastatin, gentamicin, netilmicin, ciprofloxacin, vancomycin) and cultured for 24 h. Thereafter, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, CD14 and HLA-DR expression on monocytes was assessed using flow cytometry.
  
  
  RESULTS
  All cephalosporins decreased LPS-stimulated IL-10 release. Cefuroxime and cefotaxime also decreased the expression density of the LPS recognition molecule CD14 on monocytes. An increase in LPS-stimulated IL-10 release was observed with vancomycin. A suppression of LPS-stimulated TNF-alpha and IL-10 release was observed in the presence of ciprofloxacin.
  
  
  CONCLUSIONS
  These results indicate a modulation of the expression density of CD14 on monocytes, together with a shift from a balanced to an inflammatory cytokine release pattern, by cefuroxime and cefotaxime. Vancomycin changes the response to an anti-inflammatory release pattern. After ciprofloxacin, a profound unresponsiveness of immune-competent cells to LPS stimulation is observed. Because of the critical role of a balanced innate immune response, these data may be of importance for the selection of antibiotics in septic patients.
authors.affiliation: University of the Saarland, Department of Anesthesiology and Critical Care Medicine, Homburg/Saar, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ziegeler
authors.forename: A
authors.initials: A
authors.lastname: Raddatz
authors.forename: G
authors.initials: G
authors.lastname: Hoff
authors.forename: H
authors.initials: H
authors.lastname: Buchinger
authors.forename: I
authors.initials: I
authors.lastname: Bauer
authors.forename: A
authors.initials: A
authors.lastname: Stockhausen
authors.forename: H
authors.initials: H
authors.lastname: Sasse
authors.forename: I
authors.initials: I
authors.lastname: Sandmann
authors.forename: S
authors.initials: S
authors.lastname: Hörsch
authors.forename: H
authors.initials: H
authors.lastname: Rensing
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D004731:Endotoxins; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10