Potencies of PDE4 inhibitors in attenuation of TNF-α production by human PBMCs and whole blood PBMCs were isolated from heparinized human blood, and after incubation of cells (5 × 104) with LPS (1 ng/ml) and PDE4 inhibitor or vehicle for 20 h, culture supernatants were assayed for TNF-α. Heparinized whole blood was incubated with PDE4 inhibitor or vehicle for 1 h before the addition of LPS (50 ng/ml) for 20 h; plasma was then collected and assayed for TNF-α.
IC50 Mean (95% Confidence Limits) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| EPPA-1 | Roflumilast | Roflumilast N-oxide | Cilomilast | Rolipram | |||||
| nM | |||||||||
| PBMC | 38.0 (34.1, 42.4) | 5.0 (4.6, 5.5) | 2.1 (1.5, 3.1) | 389.0 (139.5, 1085.1) | 269.2 (173.4, 417.8) | ||||
| n = 4 | n = 140 | n = 8 | n = 4 | n = 4 | |||||
| Whole blood | 91.2 (53.2, 156.5) | 19.5 (17.8, 21.3) | 20.0 (9.3, 42.8) | >5754 | 707.9 (235.9, 2124.7) | ||||
|
| n = 16 | n = 172 | n = 8 | n = 4 | n = 4 | ||||