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Open Access Research article

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

Corine E Delsing1, Mark S Gresnigt1, Jenneke Leentjens12, Frank Preijers4, Florence Allantaz Frager5, Matthijs Kox23, Guillaume Monneret5, Fabienne Venet5, Chantal P Bleeker-Rovers1, Frank L van de Veerdonk1, Peter Pickkers2, Alexandre Pachot5, Bart Jan Kullberg1 and Mihai G Netea16*

Author Affiliations

1 Department of Internal Medicine, Division of Experimental Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

2 Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

3 Department of Anaesthesiology, Radboud University Medical Center, Nijmegen, The Netherlands

4 Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

5 Joint Unit « Sepsis » Hospices Civils de Lyon–bioMérieux, Hôpital Edouard Herriot, Lyon, France

6 Department of Internal Medicine (463), Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

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BMC Infectious Diseases 2014, 14:166  doi:10.1186/1471-2334-14-166

Published: 26 March 2014

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.

Trial registration

ClinicalTrials.gov - NCT01270490

Keywords:
Immunotherapy; Interferon-gamma; Candidemia; Aspergillosis