Mesopram, a specific inhibitor of type-4
phosphodiesterase, decreases the synthesis of
tumor necrosis factor-alpha (
TNF-alpha) and
interferon-gamma (IFN-gamma). In the present study, we investigated the effect of
mesopram in
dextran sulfate sodium (DSS)-induced murine
colitis. In the preventive model,
colitis was induced by DSS simultaneously with the application of
mesopram in BALB/c mice. In the therapeutic model,
colitis was induced in BALB/c mice by DSS over 7 days. At day 8, DSS was discontinued, and treatment was started.
Mesopram was applied intraperitoneally or orally. The clinical score was calculated daily during the course of each study. Post mortem, colon length, histologic score, and expression of
TNF-alpha and IFN-gamma in colons were determined. In the preventive model,
mesopram significantly reduced the maximal clinical score, decreased colon shortening, and the histologic score. A dose finding study, using the preventive model, showed that most clinical and post mortem benefit was achieved with 50 mg/kg
mesopram compared with 2 and 10 mg/kg. In the therapeutic model, i.p.
mesopram treatment led to a significant reduction of clinical score. Both, i.p. and p.o.
mesopram significantly reversed DSS-induced colon shortening and reduced the ex vivo colonic production of IFN-gamma. We conclude that the specific type-4
phosphodiesterase inhibitor mesopram ameliorates murine
colitis both in a preventive and a therapeutic setting.