TABLE 1

Inhibition of PDE4 activity in human PMNLs by AWD 12-281 and other PDE4 inhibitors and inhibition of cytokine release in PBMC by AWD 12-281, other PDE4 inhibitors, and dexamethasone

PDE4 activity was measured by quantification of [3H]5′AMP, and concentrations that caused 50% inhibition (IC50) were determined. Values are displayed as S.E.M. in parentheses and numbers of experiments in brackets. Cytokines released by differently stimulated human PBMCs were measured by ELISA, and concentrations causing half maximum inhibition (EC50) were determined. Values are displayed as S.E.M. in round brackets and numbers of experiments in square brackets.

Compound
PDE4 Inhibition IC50
IL-2a EC50e
IL-5b EC50e
IL-5c EC50e
IL-4c ECe
TNFαd EC50e
nM
AWD 12-281 9.71 (0.51) [4] 50.0 (10.84) [4] 46.3 (7.25) [3] 77.0 (10.68) [4] 121.5 (55.04) [3] 87.9 (26.60) [3]
Rolipram 75.50 (4.56) [4] 207.0 (43.62) [4] 338.6 (32.49) [2] N.D. N.D. 322.4 (87.50) [4]
Cilomilast 17.80 (2.32) [4] 160.0 (33.03) [4] 165.3 (54.53) [2] N.D. N.D. 699.7 (179.64) [3]
RPR-73401 0.41 (0.0075) [4] N.D. 2.0 (0.19) [3] N.D. N.D. 4.97 (0.78) [4]
RS-25344-000 0.28f N.D. 0.3 (0.37) [4] N.D. N.D. 5.4 (0.75) [4]
Roflumilast 0.27 (0.02) [8] 4.7 (0.88) [4] 3.4 (1.22) [4] 6.7 (0.36) [4] 11.2 (0.78) [4] 21.2 (1.94) [3]
Dexamethasone
7.5 (0.51) [3]
2.9 (0.79) [4]
88 ± 1.6% inhibition at 10 nM [4]
59 ± 4.2% inhibition at 10 nM [4]
6.4 (1.42) [4]

  • Con A, concanavalin; N.D., not determined.

  • ↵ a PHA-P-stimulated.

  • ↵ b Concanavalin A-stimulated.

  • ↵ c Costimulated.

  • ↵ d LPS-stimulated.

  • ↵ e half-maximum inhibition.

  • ↵ f Data from Alvarez et al. (1994).