TABLE 3.
Effects of roflumilast alone or combined with formoterol on the release of TNF-α, IL-6 and CC and CXC chemokines by human bronchial explants stimulated with LPS.
| Cytokine (ng/100 mg) | LPS (1 µg/mL) | |||||
|---|---|---|---|---|---|---|
| T | R (1 nM) | R (100 nM) | F | F + R (1 nM) | F + R (100 nM) | |
| TNF-α (n = 8) | 0.54 ± 0.07 | 0.32 ± 0.10** | 0.14 ± 0.05*** | 0.36 ± 0.09* | 0.20 ± 0.06*** | 0.09 ± 0.03*** |
| 41% | 74% | 33% | 63% | 83% | ||
| CCL2 (n = 9) | 61.5 ± 11.4 | 45.8 ± 8.6** | 35.1 ± 7.6*** | 44.9 ± 8.6* | 35.6 ± 7.7*** | 27.9 ± 6.4*** |
| 25% | 43% | 27% | 42% | 55% | ||
| CCL3 (n = 9) | 7.6 ± 0.9 | 4.1 ± 1.0* | 1.9 ± 0.4*** | 5.5 ± 0.8* | 2.8 ± 0.6*** | 1.5 ± 0.3*** |
| 46% | 75% | 27% | 63% | 80% | ||
| CCL4 (n = 10) | 7.9 ± 1.6 | 4.8 ± 1.5** | 2.0 ± 0.7*** | 6.7 ± 1.5 | 3.3 ± 1.0*** | 1.6 ± 0.6*** |
| 39% | 74% | 15% | 58% | 79% | ||
| CCL5 (n = 9) | 0.19 ± 0.02 | 0.14 ± 0.03** | 0.11 ± 0.01** | 0.15 ± 0.03 | 0.11 ± 0.01** | 0.09 ± 0.01*** |
| 26% | 42% | 21% | 42% | 53% | ||
| CXCLl (n = 6) | 151.1 ± 23.8 | 116.7 ± 21.6 | 126.3 ± 32.2 | 119.6 ± 22.7 | 134.5 ± 42.5 | 105.5 ± 35.9 |
| CXCL5 (n = 6) | 16.6 ± 3.7 | 15.8 ± 3.7 | 13.7 ± 2.7 | 16.0 ± 4.0 | 15.9 ± 3.2 | 13.2 ± 1.9 |
| CXCL8 (n = 11) | 656.4 ± 106.7 | 529.6 ± 79.3* | 477.8 ± 62.7** | 613.8 ± 97.1 | 531.5 ± 80.3 | 434.9 ± 80.2** |
| 20% | 25% | 6% | 19% | 34% | ||
| CXCL9 (n = 13) | 4.8 ± 0.9 | 3.6 ± 0.8** | 2.7 ± 0.6*** | 4.3 ± 0.9 | 2.9 ± 0.6*** | 2.3 ± 0.5*** |
| 25% | 43% | 10% | 39% | 48% | ||
| IL-6 (n = 9) | 373.2 ± 78.3 | 323.8 ± 85.6 | 241.2 ± 44.1** | 281.4 ± 52.2* | 284.2 ± 69.8 | 208.2 ± 59.3*** |
| 35% | 25% | 44% | ||||
Bronchial explants were pre-treated with vehicle (T), roflumilast (R: 1 nM or 100 nM), formoterol (F: 10 nM) or a combination of formoterol and roflumilast (F + R) before being stimulated with LPS (1 µg/mL) for 24 h. Data are quoted as the mean ± SEM for the number of independent experiments indicated in brackets. *p < 0.05; **p < 0.01; ***p < 0.001 vs. LPS (T). The significant or relevant results (in italics) are also expressed as the percentage inhibition vs T (LPS alone).