PT  - JOURNAL ARTICLE
AU  - Gunther Hartmann
AU  - Christoph Bidlingmaier
AU  - Britta Siegmund
AU  - Stefan Albrich
AU  - Johannes Schulze
AU  - Katharina Tschoep
AU  - Andreas Eigler
AU  - Hans Anton Lehr
AU  - Stefan Endres
TI  - Specific Type IV Phosphodiesterase Inhibitor Rolipram Mitigates Experimental Colitis in Mice
DP  - 2000 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 22--30
VI  - 292
IP  - 1
4099  - http://jpet.aspetjournals.org/content/292/1/22.short
4100  - http://jpet.aspetjournals.org/content/292/1/22.full
SO  - J Pharmacol Exp Ther2000 Jan 01; 292
AB  - The specific type IV phosphodiesterase inhibitor rolipram is a potent suppressor of tumor necrosis factor-α (TNF) synthesis. We examined the efficacy of rolipram for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulfate sodium in their drinking water continuously for up to 11 days. Colitis was quantified by a clinical activity score assessing weight loss, stool consistency, and rectal bleeding (range from 0 to 4); by colon length; by a semiquantitative histologic score (range from 0 to 6); and by detecting TNF concentration in colonic tissue by enzyme-linked immunosorbent assay. In a first protocol, rolipram (10 mg/kg b.wt./day i.p.) was started on the same day as dextran sulfate sodium. Rolipram reduced the clinical activity of colitis (score 1.1 ± 0.3) compared with mice that did not receive rolipram (2.4 ± 0.4; P = .041). Rolipram also partially reversed the reduction of colon length (without rolipram, 12.4 ± 0.3 cm; with rolipram, 15.4 ± 0.7 cm;P = .004) and improved the histologic score (1.5 ± 0.6 in rolipram-treated mice versus 4.6 ± 0.5;P = .020). Rolipram suppressed colonic tissue TNF concentrations. The beneficial effect of rolipram was confirmed in a second protocol in which dextran sulfate sodium exposure was discontinued on day 7 and rolipram was administered from day 8 through day 15. These three series of experiments on a total of 153 mice documented the efficacy of rolipram in both the prevention and treatment of experimental colitis. The American Society for Pharmacology and Experimental Therapeutics