title: Antifungal antibiotics modulate the pro-inflammatory cytokine production and phagocytic activity of human monocytes in an in vitro sepsis model.
abstract: OBJECTIVE
  The incidence of secondary systemic fungal infections has sharply increased in bacterial septic patients. Antimycotics exhibit immunomodulatory properties, yet these effects are incompletely understood in secondary systemic fungal infections following bacterial sepsis. We investigated a model of systemic inflammation to determine whether antimycotics (liposomal amphotericin B (L-AMB), itraconazol (ITC), and anidulafungin (ANI)) modulate the gene and protein expression as well as the phagocytic activity of lipopolysaccharide (LPS)-stimulated human monocytes.
  
  
  METHODS
  THP-1 monocytes were incubated with L-AMB, ITC or ANI and LPS. Gene expression levels of cytokines (TNF-<alpha>, IL-1<beta>, IL-6, and IL-10) were measured after 2h, 6h, and 24h. Cytokine protein levels were evaluated after 24h and phagocytic activity was determined following co-incubation with Escherichia coli.
  
  
  RESULTS
  All antimycotics differentially modulated the gene and protein expression of cytokines in sepsis-like conditions. In the presence of LPS, we identified L-AMB as immunosuppressive, whereas ITC demonstrated pro-inflammatory properties. Both compounds induced remarkably less phagocytosis.
  
  
  CONCLUSIONS
  Our study suggests that antimycotics routinely used in septic patients alter the immune response in sepsis-like conditions by modulating cytokine gene and protein expression levels and phagocytic activity. Future treatment strategies should consider the immune status of the host and apply antimycotics accordingly in bacterial septic patients with secondary fungal infections.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany. Electronic address: s.muenster@gmail.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Muenster
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bode
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany; Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Diedrich
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jahnert
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Weisheit
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Folkert
authors.initials: F
authors.lastname: Steinhagen
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Stilla
authors.initials: S
authors.lastname: Frede
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.affiliation: Institute of Physiology II, University of Bonn, Bonn, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Meyer
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Boehm
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Baumgarten
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D054714:Echinocandins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D017964:Itraconazole / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D018805:Sepsis / Q000473:pathology*
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D054714:Echinocandins; D007166:Immunosuppressive Agents; D017964:Itraconazole; D000666:Amphotericin B; D000077612:Anidulafungin
keywords: Amphotericin B; Anidulafungin; Immunomodulation; Itraconazole; Phagocytosis; Sepsis