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-gamma) 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-gamma (rIFN-gamma, 100 mu g s.c., thrice a week) for 2 weeks in addition to standard antifungal therapy. Results: Recombinant IFN-gamma 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-gamma can restore immune function in fungal sepsis patients, warranting future clinical studies to assess its potential clinical benefit.