Related Experiment Videos
Selective type IV phosphodiesterase inhibitors prevent IL-4-induced IgE production by human peripheral blood
O Coqueret1, E Boichot, V Lagente
1Laboratoire de Pharmacodynamie et Pharmacologie Moléculaire INSERM U 456, Faculté des Sciences Pharmaceutiques et Biologiques Université de Rennes, France.
Background:
Selective type IV phosphodiesterase (PDE) inhibitors elicit anti-inflammatory and bronchodilatory activities in vitro and in vivo which suggest that these drugs could provide a new therapeutic approach for asthma treatment.
Objective:
Regarding the role of IgE production in allergic and inflammatory reactions of the airways, we investigated the effect of selective PDE inhibitors on IL-4-driven IgE production by peripheral blood mononuclear cells (PBMC) or by purified B lymphocytes.
Methods:
PBMC or purified B lymphocytes from non-allergic donors were stimulated for 13 days with IL-4 (100 U/mL) in the presence or in the absence of selective PDE inhibitors. IgE production is evaluated by an ELISA technique.
Results:
The selective PDE IV inhibitors, rolipram and Ro 20-1724 (10 microM), inhibit IL-4-induced IgE production by PBMC, but not by purified B lymphocytes. No modification of the IgE production was noted with the selective PDE III inhibitors, milrinone and SK&F 94-836, or the selective PDE V inhibitor, SK&F 96-231 (10 microM). Flow cytometry experiments showed that the effect of Rolipram could not be explained by the inhibition of the cell surface expression of the IL-4 receptor. Similarly, no significant effect of PDE IV inhibitors was observed on PHA-induced cell proliferation. The incubation of monocytes only with rolipram was sufficient to achieve a significant reduction of IgE production induced by IL-4.
Conclusion:
Taken together, these results indicate that PDE IV inhibitors reduce IL-4-induced IgE production by PBMC and suggest that the inhibition of IgE production could be explained by a failure of monocytes to provide the necessary costimulatory signals.