Selective type IV phosphodiesterase inhibitors prevent IL-4-induced IgE production by human peripheral blood mononuclear cells

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 ISE 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 mu M), 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 mu M). 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 TV inhibitors reduce IL-4-induced IEE 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.