Rieder, Florian and Siegmund, Britta and Bundschuh, Daniela S. and Lehr, Hans-Anton and Endres, Stefan and Eigler, Andreas (2013) The Selective Phosphodiesterase 4 Inhibitor Roflumilast and Phosphodiesterase 3/4 Inhibitor Pumafentrine Reduce Clinical Score and TNF Expression in Experimental Colitis in Mice. PLOS ONE, 8 (2): e56867. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Objective: The specific inhibition of phosphodiesterase (PDE) 4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. Methods: The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-gamma (IFN gamma) production and CD69 expression. Results: Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-alpha (TNF alpha) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNF alpha production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFN gamma compared to no treatment in vivo. Conclusions: These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; INFLAMMATORY-BOWEL-DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; SODIUM-INDUCED COLITIS; PDE4 INHIBITOR; ULCERATIVE-COLITIS; MURINE COLITIS; FACTOR-ALPHA; IN-VITRO; ROLIPRAM; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 07:43 |
| Last Modified: | 24 Apr 2020 07:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17123 |
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