Effect of selected PDE4 inhibitors on human and mouse TNFα production in vivo
| Compound | hPDE4 (IC50 nM) | Treatment (mg/kg, p.o.) | TNFα Inhibition (pg/ml, Mean ± S.E.) | |
|---|---|---|---|---|
| Human | Mouse | |||
| Expt. I | Vehicle (N = 7) | 514.7 ± 68.8 | 694.8 ± 19.5 | |
| SB 207499 | 115 | 50 (N = 5) | 108.6 ± 22.11-a | 209.0 ± 19.51-a |
| −78.9% | −69.9% | |||
| Expt. II | Vehicle (N = 8) | 163.7 ± 16.7 | 444.3 ± 16.3 | |
| Denbufylline | 290 | 50 (N = 5) | 30.5 ± 10.81-a | 98.3 ± 11.31-a |
| −81.4% | −77.9% | |||
| Tibenelast | 134 | 50 (N = 5) | 62.3 ± 15.11-a | 277.1 ± 17.01-b |
| −61.2% | −37.6% | |||
| Expt. III | Vehicle (N = 7) | 286.8 ± 71.0 | 286.1 ± 32.7 | |
| R-rolipram | 310 | 30 (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.