Interferon-gamma as adjunctive immunotherapy for invasive fungal infections

Ref ID: 19445

Author:

M. Gresnigt,1 J. Leentjens,2 C. E. Delsing,3 F. Allantaz Frager,4
M. Kox,2 G. Monneret,4 F. Venet,4 C. P. Bleeker-Rovers,3 A.
Pachot,4 B. J. Kullberg3 and M. G. Netea3

Author address:

1Radboud University Nijmegen Medical Centre, the Netherlands;
2Radboud University Nijmegen Medical Centre Department of
Intensive Care Medicine, the Netherlands; 3Radboud University
Nijmegen Medical Centre, Department of Medicine, the
Netherlands

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives The incidence of fungal infections is increasing at an
alarming rate, despite development of new classes of antifungal agents.
Invasive fungal infections remain associated with unacceptable high
mortality rates and represent a major cause of death worldwide. The
evolution of mechanisms for significant resistance to the current anti-
fungal drugs further emphasizes the need for novel approaches to treat
invasive fungal infections. As invasive fungal infections are most com-
monly observed in individuals with immune defects or dysfunction and
the number of immunocompromised patients is steadily increasing.
Adjunctive immunotherapy, to improve anti-fungal host defense, is
therefore an attractive strategy to improve the outcome of patients with
disseminated fungal infections.
Methods In a case series we included eight patients with severe
invasive Candida and/or Aspergillus infections who were treated with
recombinant IFNc for 2 weeks. From these patients blood was drawn
to measure the ex-vivo responsiveness of to fungal stimulation, HLA-
DR expression and lymphocyte subsets.
Results Treatment with IFNc significantly boosted ex-vivo IL-1b and
TNFa response to C. albicans and LPS at the first days after initiation of
treatment. Additionally, an increase in the capacity to induce T-cell
cytokines IL-17 and IL-22 was observed after initiation of IFNc ther-
apy. Treatment with IFNc also modulated the leucocyte subsets in the
peripheral blood. We were unable to find significant changes in HLA-
DR expression which might be explained by the fact that most of the
patients were not immunoparalysed. However, patients that demon-
strated decreased HLA-DR upon inclusion showed a trend towards
increasing monocytes HLA-DR expression after IFNc treatment.
Conclusion Collectively these data provide a first immunological
proof-of-principle that adjunctive immunotherapy with IFNg might
improve the outcome invasive fungal infections. Yet still, larger clini-
cal trials are warranted to assess this possibility.

Abstract Number: p388

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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