title: Roflumilast, a Type 4 Phosphodiesterase Inhibitor, Shows Promising Adjunctive, Host-Directed Therapeutic Activity in a Mouse Model of Tuberculosis.
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).
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Mariama C
authors.initials: MC
authors.lastname: Maiga
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Bintou Ahmadou
authors.initials: BA
authors.lastname: Ahidjo
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali.
authors.forename: Mamoudou
authors.initials: M
authors.lastname: Maiga
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Howard Hughes Medical Institute, Chevy Chase, Maryland, USA wbishai1@jhmi.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D007538:Isoniazid / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D016019:Survival Analysis; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000631:Aminopyridines; D000995:Antitubercular Agents; D001549:Benzamides; D003521:Cyclopropanes; D053583:Interleukin-1beta; D058988:Phosphodiesterase 4 Inhibitors; D014409:Tumor Necrosis Factor-alpha; C424423:Roflumilast; D007371:Interferon-gamma; D007538:Isoniazid