Efficacy of gene-therapy based on adenovirus encoding granulocyte-macrophage colony-stimulating factor in drug-sensitive and drug-resistant experimental pulmonary tuberculosis. (September 2016)

• Record Type: Journal Article
• Authors: Francisco-Cruz, Alejandro; Mata-Espinosa, Dulce; Ramos-Espinosa, Octavio; Marquina-Castillo, Brenda; Estrada-Parra, Sergio; Xing, Zhou; Hernández-Pando, Rogelio
• Is Part Of: Tuberculosis. Volume 100(2016)
• Page Start: 5
• Page End: 14
• Publication Date: 2016-09
• Subjects: Adjunct treatment -- Tuberculosis -- Multidrug-resistant tuberculosis -- Granulocyte-macrophage colony-stimulating factor; 616.995
• DOI: 10.1016/j.tube.2016.05.015
• Languages: English
• ISSNs: 1472-9792

Abstract

Summary: Tuberculosis (TB), although a curable disease, remains a major cause of morbidity and mortality worldwide. It is necessary to develop a short-term therapy with reduced drug toxicity in order to improve adherence rate and control disease burden. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be a key cytokine in the treatment of pulmonary TB since it primes the activation and differentiation of myeloid and non-myeloid precursor cells, inducing the release of protective Th1 cytokines. In this work, we administrated by intratracheal route recombinant adenoviruses encoding GM-CSF (AdGM-CSF). This treatment produced significant bacterial elimination when administered in a single dose at 60 days of infection with drug sensitive or drug resistant Mtb strains in a murine model of progressive disease. Moreover, AdGM-CSF combined with primary antibiotics produced more rapid elimination of pulmonary bacterial burdens than conventional chemotherapy suggesting that this form of treatment could shorten the conventional treatment.