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  3. Medizin - Open Access LMU - Teil 20/22 Podcast
  4. The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.
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. 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-γ (IFNγ)
production and CD69 expression. Roflumilast treatment resulted in
dose-dependent improvements of clinical score (weight loss, stool
consistency and bleeding), colon length, and local tumor necrosis
factor-α (TNFα) 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 TNFα
production. In vitro stimulated splenocytes after in vivo treatment
with pumafentrine showed a significantly lower state of activation
and production of IFNγ compared to no treatment in vivo. These
series of experiments document the ameliorating effect of
roflumilast and pumafentrine on the clinical score and TNF
expression of experimental colitis in mice.

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„The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.“

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