title: Effects of anidulafungin and voriconazole, singly and in combination, on cytokine/chemokine production by human monocyte-derived macrophages infected with Candida glabrata or activated by lipopolysaccharide.
abstract: BACKGROUND
  Candida glabrata causes infections associated with severe sepsis, production of high concentrations of cytokines/chemokines, and high mortality. This study describes the effects of anidulafungin (ANF) and voriconazole (VRC), singly and in combination, on the production of eight cytokines/chemokines by human monocyte-derived macrophages (MDM) infected with C. glabrata or activated by lipopolysaccharide (LPS).
  
  
  METHODS
  MDM monolayers were established, infected with C. glabrata or activated with LPS, and then treated with high or low concentrations of ANF, VRC, or both. Cytokine/chemokine levels in MDM supernatants were determined.
  
  
  RESULTS
  Levels of cytokines/chemokines were significantly elevated in supernatants of infected or LPS-activated MDM. Except for interleukin-10, all significant decreases in cytokine/chemokine concentrations (p < 0.01) occurred in supernatants of infected MDM treated with high concentrations of ANF or ANF + VRC.
  
  
  CONCLUSIONS
  Decreases in cytokine/chemokine levels in supernatants of infected MDM treated with high concentrations of ANF or ANF + VRC suggest that similar treatment could improve survival in patients with severe, invasive C. glabrata infections and markedly elevated levels of serum cytokines/chemokines.
authors.affiliation: Stratton Veterans Affairs Medical Center, Albany, NY, USA.
authors.forename: Aldona L
authors.initials: AL
authors.lastname: Baltch
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.forename: William J
authors.initials: WJ
authors.lastname: Ritz
authors.forename: Nancy
authors.initials: N
authors.lastname: Andersen
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Bopp
authors.forename: Phyllis B
authors.initials: PB
authors.lastname: Michelsen
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Carlyn
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Smith
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000472:pathogenicity*; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D018925:Chemokines; D016207:Cytokines; D054714:Echinocandins; D008070:Lipopolysaccharides; D011743:Pyrimidines; D014230:Triazoles; D000077612:Anidulafungin; D065819:Voriconazole