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 approa ch for asthma treatment.Objective Regarding the role of IgE production in allergic and inflammatory reactions of the airways, we investigate d the effect of selective PDE inhibitors on IL-4-driven ISE production by peripheral blood mononuclear cells (PBMC) or by purified B lymphoc ytes. 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, rolipr am and Ro 20-1724 (10 mu M), inhibit IL-4-induced IgE production by PB MC, but not by purified B lymphocytes. No modification of the IgE prod uction 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 no t 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 mono cytes only with rolipram was sufficient to achieve a significant reduc tion of IgE production induced by IL-4. Conclusion Taken together, the se results indicate that PDE TV inhibitors reduce IL-4-induced IEE pro duction by PBMC and suggest that the inhibition of IgE production coul d be explained by a failure of monocytes to provide the necessary cost imulatory signals.