title: Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series.
abstract: BACKGROUND
  Invasive fungal infections are very severe infections associated with high mortality rates, despite the availability of new classes of antifungal agents. Based on pathophysiological mechanisms and limited pre-clinical and clinical data, adjunctive immune-stimulatory therapy with interferon-gamma (IFN-γ) may represent a promising candidate to improve outcome of invasive fungal infections by enhancing host defence mechanisms.
  
  
  METHODS
  In this open-label, prospective case series, we describe eight patients with invasive Candida and/or Aspergillus infections who were treated with recombinant IFN-γ (rIFN-γ, 100 μg s.c., thrice a week) for 2 weeks in addition to standard antifungal therapy.
  
  
  RESULTS
  Recombinant IFN-γ treatment in patients with invasive Candida and/or Aspergillus infections partially restored immune function, as characterized by an increased HLA-DR expression in those patients with a baseline expression below 50%, and an enhanced capacity of leukocytes from treated patients to produce proinflammatory cytokines involved in antifungal defence.
  
  
  CONCLUSIONS
  The present study provides evidence that adjunctive immunotherapy with IFN-γ can restore immune function in fungal sepsis patients, warranting future clinical studies to assess its potential clinical benefit.
  
  
  BACKGROUND
  ClinicalTrials.gov--NCT01270490.
authors.forename: Corine E
authors.initials: CE
authors.lastname: Delsing
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gresnigt
authors.forename: Jenneke
authors.initials: J
authors.lastname: Leentjens
authors.forename: Frank
authors.initials: F
authors.lastname: Preijers
authors.forename: Florence Allantaz
authors.initials: FA
authors.lastname: Frager
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.forename: Chantal P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pachot
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.affiliation: Department of Internal Medicine, Division of Experimental Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. mihai.netea@radboudumc.nl.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D000328:Adult; D000368:Aged; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D058365:Candidiasis, Invasive / Q000188:drug therapy*; D003131:Combined Modality Therapy; D054714:Echinocandins / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D000077612:Anidulafungin