Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection

Aspergillus terreus causes invasive aspergillosis (IA) in immunocompromised patients. Treatment is complicated by intrinsic resistance to amphotericin B and thereby contributing to a high mortality. Therefore, we conducted in vitro studies to investigate the effectivity of adjunctive recombinant interferon-gamma immunotherapy. We describe a pediatric patient with A. terreus IA who received adjunctive recombinant interferon-gamma (rIFN gamma) immunotherapy. In vitro studies were conducted to investigate the capacity of rIFN gamma to improve antifungal host defense in terms of fungal killing ability and the release of pro-inflammatory cytokines in cells of the patient as well as healthy controls. An 8-year-old female pediatric patient with leukemia developed A. terreus IA. She clinically deteriorated and had high serum galactomannan levels despite broad antifungal therapy. Therefore, adjunctive immune stimulatory therapy with rIFN gamma was initiated. After 3 weeks of treatment, galactomannan levels decreased and the patient clinically showed improvement. Addition of rIFN gamma boosted the capacity of monocytes of healthy volunteers to mount TNF alpha and IL-1 beta cytokine responses to Escherichia coli LPS, and increased TNF alpha response to both A. terreus and Aspergillus fumigatus. Monocytes isolated from the patient's blood demonstrated a similar augmented cytokine induction in response to rIFN gamma. In addition, rIFN gamma increased the capacity of monocytes from healthy volunteers as well as monocytes from the patient to kill A. terreus spores. Adjuvant immunotherapy with rIFN gamma might be a promising additional treatment strategy that could be used to improve outcome in patients with refractory invasive A. terreus infections or other resistant invasive Aspergillus infections.