TABLE 2.
Effect of oral administration of roflumilast on CFUs in the lungs and inflammatory markers in the BALF.
| Vehicle | Roflumilast | |
|---|---|---|
| Total cells (106/ml) | 2,49 ± 2,1 | 1,57 ± 1,2 (p = 0,04) |
| Neutrophils (106/ml) | 1,84 ± 1,0 | 1,04 ± 1,14 (p = 0,05) |
| Macrophages (106/ml) | 0,52 ± 0,2 | 0,48 ± 0,4 (p = 0,41) |
| Interleukin-1β (pg/ml) | 114,3 ± 51,2 | 80,27 ± 69,0 (p = 0,10) |
| TNF-α (pg/ml) | 1506,9 ± 263,9 | 1184,4 ± 392,1 (p = 0.008) |
| CXCL-1 (KC) (pg/ml) | 19,0 ± 9,0 | 13,7 ± 11,1 (p = 0,12) |
| Free DNA (μ/ml) | 2,2 ± 2,3 | 1,5 ± 1,4 (p = 0,19) |
| CFU - lung (x 1,000) | 49,6 ± 52,9 | 55,9 ± 91,7 (p = 0,47) |
| Total proteins (mg/ml) | 558,7 ± 208,3 | 445,8 ± 119,3 (p = 0,07) |
C57BL/6 male mice (8–10 weeks of age) were infected i.t. with 1 × 106 CFUs of MDR-RP73 embedded in agar beads. Mice (11 per group of treatment) were treated by gavage with roflumilast (5 mg/kg/day) or placebo (4,4% DMSO in saline), with the starting dose administered 2 h before infection and the last 2 h before killing. 5 days after infection, mice were sacrificed, the BALF was collected, and mouse lungs were recovered, homogenized, and plated to determine the bacterial load. Counts of total cells, neutrophils, and macrophages, as well as levels of cytokines and total protein, were evaluated in the BALF. Statistical differences between roflumilast- and vehicle-treated animals were analyzed by Student’s t-test.