Table 1

Effect of selected PDE4 inhibitors on human and mouse TNFα production in vivo

CompoundhPDE4 (IC50 nM)Treatment (mg/kg, p.o.)TNFα Inhibition (pg/ml, Mean ± S.E.)
HumanMouse
Expt. IVehicle (N = 7)514.7  ± 68.8694.8  ± 19.5
SB 20749911550  (N = 5)108.6  ± 22.11-a 209.0  ± 19.51-a
−78.9%−69.9%
Expt. IIVehicle (N = 8)163.7  ± 16.7444.3  ± 16.3
Denbufylline29050  (N = 5)30.5  ± 10.81-a 98.3  ± 11.31-a
−81.4%−77.9%
Tibenelast13450  (N = 5)62.3  ± 15.11-a 277.1  ± 17.01-b
−61.2%−37.6%
Expt. IIIVehicle (N = 7)286.8  ± 71.0286.1  ± 32.7
R-rolipram31030  (N = 4)68.3  ± 18.5c 93.3  ± 5.61-a
−76.2%−67.4%
  • Balb/c mice were injected with human monocytes as described, drug was administered at doses indicated and LPS was injected i.p. Two hours later, the animals were euthanized and a peritoneal washout obtained for subsequent ELISA analysis. Values for inhibition of human recombinant PDE4A are from previously published results (Barnetteet al., 1995; Torphy et al., 1992, 1997).

  • 1-a P <.001.

  • 1-b P < .01.