Table 3.

Potency and efficacy of the PDE4 inhibitors roflumilast and roflumilast N-oxide to reduce TNF-α, CCL2, CCL3, CCL4 and CXCL10 release from LPS-stimulated human lung macrophages in presence and absence of 10 nM PGE₂

PDE4 inhibitor		Roflumilast		Roflumilast N-oxide
Calculated parameter		EC50	Efficacy	EC50	Efficacy	Inhibition at 1 nM
Analyte	Additive	nM [CI 95]	%	nM [CI 95]	%	%
TNF-α	Vehicle	0.1 [0.03–0.5]	38 ± 3	0.4 [0.1–1.4]	45 ± 3	31 ± 8
	10 nM PGE2	0.2 [0.06–0.4]	57 ± 3	0.3 [0.1–0.9]	60 ± 4	43 ± 8
CCL2	Vehicle	0.2 [0.09–0.6]	58 ± 3	1.0 [0.4–2.2]	63 ± 3	30 ± 6
	10 nM PGE2	0.2 [0.06–0.6]	63 ± 4	0.7 [0.3–1.5]	70 ± 3	42 ± 6
CCL3	Vehicle	0.5 [0.07–3.1]	29 ± 3	1.5 [0.5–4.4]	32 ± 2	13 ± 2
	10 nM PGE2	0.3 [0.09–1.0]	49 ± 3	0.7 [0.2–2.3]	48 ± 3	29 ± 4
CCL4	Vehicle	0.5 [0.1–2.5]	32 ± 3	0.4 [0.04–4.3]	26 ± 4	17 ± 6
	10 nM PGE2	0.7 [0.08–2.8]	45 ± 3	0.6 [0.2–2.0]	46 ± 3	29 ± 3
CXCL10	Vehicle	0.1 [0.04–0.4]	49 ± 3	1.6 [0.2–10]	45 ± 6	18 ± 9
	10 nM PGE2	0.1 [0.02–0.6]	60 ± 5	1.0 [0.2–3.5]	58 ± 5	30 ± 11

Values of EC₅₀ are shown with 95% confidence intervals (CI 95). The maximum efficacy (mean ± SEM) and the percentage of inhibition achieved by roflumilast N-oxide at 1 nM (mean ± SEM) were calculated from concentration-dependent inhibition curves given in Figure 2 and 3. TNF-α, CCL2, 3 or 4 and CXCL10 release in presence or absence of 10 nM PGE₂ were both set as 100%. Effects of 10 nM PGE₂ on the release of the chemokines and cytokines are given in the text.