Pharmacologic inhibition of host phosphodiesterase-4 improves isoniazid mediated clearance of Mycobacterium tuberculosis

In this study, we evaluated the PK/PD and explored the efficacy of a PDE4 inhibitor, CC-11050 in a murine model of Mtb infection. Infected mouse lungs with or without CC-11050 treatment was also used to interrogate genome-wide transcriptional changes. Standard aerosol infection of mice with MtbCDC1551, followed by enumeration of lung bacterial load, pathology and transcriptional changes were monitored upto 112 days post infection. Mice were infected with Mtb and treatment with CC11050 was started at 14 days post-infection. Uninfected mice were included as control. At 28 days post-infection, mice from all 3 groups (uninfected, Mtb-infected untreated or CC11050 treated) were euthanized and lung tissue was collected to isolate total RNA and used in microarray experiments. (N=4 per group)