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Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response To Pulmonary Tuberculosis In A Rabbit Model, Selvakumar Subbian, Liana Tsenova, Jennifer Holloway, Blas Peixoto, Paul O'Brien, Veronique Dartois, Vikram Khetani, Jerome B. Zeldis, Gilla Kaplan
Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response To Pulmonary Tuberculosis In A Rabbit Model, Selvakumar Subbian, Liana Tsenova, Jennifer Holloway, Blas Peixoto, Paul O'Brien, Veronique Dartois, Vikram Khetani, Jerome B. Zeldis, Gilla Kaplan
Publications and Research
Objectives: Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB).We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection.
Methods: A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with orwithout CC-11050, starting at fourweeks post infection. The …