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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).
AuthorsMariama C Maiga, Bintou Ahmadou Ahidjo, Mamoudou Maiga, William R Bishai
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 12 Pg. 7888-90 (Dec 2015) ISSN: 1098-6596 [Electronic] United States
PMID26438491 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Aminopyridines
  • Antitubercular Agents
  • Benzamides
  • Cyclopropanes
  • Interleukin-1beta
  • Phosphodiesterase 4 Inhibitors
  • Tumor Necrosis Factor-alpha
  • Roflumilast
  • Interferon-gamma
  • Isoniazid
Topics
  • Aminopyridines (pharmacology)
  • Animals
  • Antitubercular Agents (pharmacology)
  • Benzamides (pharmacology)
  • Cyclopropanes (pharmacology)
  • Disease Models, Animal
  • Female
  • Interferon-gamma (biosynthesis, immunology)
  • Interleukin-1beta (biosynthesis, immunology)
  • Isoniazid (pharmacology)
  • Lung (drug effects, immunology, microbiology)
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis (drug effects, growth & development)
  • Phosphodiesterase 4 Inhibitors (pharmacology)
  • Survival Analysis
  • Tuberculosis, Pulmonary (drug therapy, immunology, microbiology, mortality)
  • Tumor Necrosis Factor-alpha (biosynthesis, immunology)

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