Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series

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. TRIAL REGISTRATION ClinicalTrials.gov--NCT01270490.