Abstract
With phosphodiesterase inhibitors (PDE-Is) showing significant promise in shortening tuberculosis treatment, we assessed the effect of roflumilast, an FDA-approved type 4 PDE-I, in both acute and chronic murine models of tuberculosis. Alone, roflumilast had no effect on lung bacillary burden and mortality. However, when roflumilast was used in combination with isoniazid, a reduction in lung bacillary burden was observed. These data suggest that roflumilast may be a good candidate for tuberculosis host-directed therapy (HDT).
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, N.I.H., Intramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aminopyridines / pharmacology*
-
Animals
-
Antitubercular Agents / pharmacology*
-
Benzamides / pharmacology*
-
Cyclopropanes / pharmacology
-
Disease Models, Animal
-
Female
-
Interferon-gamma / biosynthesis
-
Interferon-gamma / immunology
-
Interleukin-1beta / biosynthesis
-
Interleukin-1beta / immunology
-
Isoniazid / pharmacology
-
Lung / drug effects*
-
Lung / immunology
-
Lung / microbiology
-
Mice
-
Mice, Inbred BALB C
-
Mycobacterium tuberculosis / drug effects*
-
Mycobacterium tuberculosis / growth & development
-
Phosphodiesterase 4 Inhibitors / pharmacology*
-
Survival Analysis
-
Tuberculosis, Pulmonary / drug therapy*
-
Tuberculosis, Pulmonary / immunology
-
Tuberculosis, Pulmonary / microbiology
-
Tuberculosis, Pulmonary / mortality
-
Tumor Necrosis Factor-alpha / biosynthesis
-
Tumor Necrosis Factor-alpha / immunology
Substances
-
Aminopyridines
-
Antitubercular Agents
-
Benzamides
-
Cyclopropanes
-
Interleukin-1beta
-
Phosphodiesterase 4 Inhibitors
-
Tumor Necrosis Factor-alpha
-
Roflumilast
-
Interferon-gamma
-
Isoniazid