IL-1 BLOCKADE AS A POTENTIAL THERAPEUTIC TARGET IN ASPERGILLOSIS

Ref ID: 19530

Author:

A De Luca1*, RG Iannitti1, M Borghi1, M Puccetti1, C Galosi1, V Oikonomou1, G Renga1,
A Casagrande1,2, F van de Veerdonk3, L Romani1

Author address:

1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
2Istituto Superiore di Sanita`, Roma, Italy
3Department of Medicine, Radboud University Nijmegen Medical Center, The Netherlands

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Aspergillosis is a life-threatening disease that occurs in immunodepressed patients when infected
with Aspergillus fumigatus. The progressive decline of pulmonary function is due to a vicious
cycle of airways infection and inflammation. Intracellular danger sensing protein complexes
called inflammasomes have been identified and functionally characterized in inflammatory and
non-iflammatory cells, with their relevance to airway diseases. We hypothesized that the heighten
inflammatory response due to inflammasome activation could be responsible for life-threatening
bacterial and fungal infections in Chronic granulomatous disease (CGD) or Cystic Fibrosis (CF)
and that blocking IL-1 receptor could improve inflammation in both Chronic granulomatous disease
(CGD) or Cystic Fibrosis (CF).
Methods:
CGD or CF mice were infected with A. fumigatus and treated with anakinra (a recombinant form
of the naturally occurring IL-1 receptor antagonist) daily. Mice were monitored for survival, local
fungal growth, inflammatory cell recruitment and lung histopathology as well as parameters of
inflammasome activation.
Results:
We found that the heightened inflammatory response to A. fumigatus was associated with an increased
activation of the inflammasome and production of IL-1β in experimental CGD and CF. Anakinra
successfully controlled inflammasome-dependent IL-1β production in response to infectious or
danger signals in CGD and CF mice, an activity to which the restoration of autophagy greatly
contributed.
Conclusion:
Abnormal activation of inflammasome-dependent mechanisms are demonstrable in CGD and CF,
such that blocking IL-1 could be a potential therapeutic option to dampen pathogenic inflammation
in CGD or CF.

Abstract Number: 57

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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