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Combined itraconazole-pentoxifylline treatment promptly reduces lung fibrosis induced by chronic pulmonary paracoccidioidomycosis in mice.
MedLine Citation:
PMID:  20851204     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Fibrosis is a severe and progressive sequel of many pulmonary diseases, has no effective therapy at present and, consequently, represents a serious health problem. In Latin America, chronic pulmonary paracoccidioidomycosis (PCM) is one of the most important, prevalent and systemic fungal diseases that allows the development of lung fibrosis, with the additional disadvantage that this sequel may appear even after an apparently successful course of antifungal therapy. In this study, was propose the pentoxifylline as complementary treatment in the pulmonary PCM due to its immunomodulatory and anti-fibrotic properties demonstrated in vitro and in vivo in liver, skin and lung. Our objective was to investigate the possible beneficial effects that a combined antifungal (Itraconazole) and immunomodulatory (Pentoxifylline) therapy would have in the development of fibrosis in a model of experimental chronic pulmonary PCM in an attempt to simulate the naturally occurring events in human patients. Two different times post-infection (PI) were chosen for starting therapy, an "early time" (4 weeks PI) when fibrosis was still absent and a "late time" (8 weeks PI) when the fibrotic process had started. Infected mice received the treatments via gavage and were sacrificed during or upon termination of treatment; their lungs were then removed and processed for immunological and histopathologic studies in order to assess severity of fibrosis. When pulmonary paracoccidioidomycosis had evolved and reached an advanced stage of disease before treatment began (as normally occurs in many human patients when first diagnosed), the combined therapy (itraconazole plus pentoxifylline) resulted in a significantly more rapid reduction of granulomatous inflammation and pulmonary fibrosis, when compared with the results of classical antifungal therapy using itraconazole alone.
Authors:
Tonny W Naranjo; Damaris E Lopera; Lucy R Diaz-Granados; Jhon J Duque; Angela Restrepo M; Luz E Cano
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Publication Detail:
Type:  Journal Article     Date:  2010-09-17
Journal Detail:
Title:  Pulmonary pharmacology & therapeutics     Volume:  24     ISSN:  1522-9629     ISO Abbreviation:  Pulm Pharmacol Ther     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9715279     Medline TA:  Pulm Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  81-91     Citation Subset:  IM    
Copyright Information:
Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Unidad de Micología Médica y Experimental, Corporación para Investigaciones Biológicas, Medellín, Colombia; Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, Medellín, Colombia.
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