Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors

Background: Both glucocorticosteroids and phosphodiesterase (PDE) type 4 inhibitors have modulatory effects on PBMC cytokine secretion, In this study se compared the effect of glucocorticoids and PDE inhibitors on IL-10 and TNF-alpha production by PBMCs from nonatopic versus atopic individuals. Methods: PBMCs were incubated with glucocorticoids (beclomethasone dipropionate and mometasone furoate) or media alone for 24 hours. PDE type 4 inhibitors (Ro20-1724 and rolipram) were then added to the cells preincubated with media. After stimulation with PHA, incubation was continued for 48 hours, The cytokine content of the cell supernatants was determined by ELISA. Results: PDE-4 inhibitors and glucocorticoids caused a concentration-dependent inhibition of the secretion of both TNF-alpha and IL-10. PDE-4 inhibitors were over 20 times more potent in suppressing cytokine secretion by PBMCs from atopic than nonatopic donors, and approximately 5 times more potent in preventing TNF-alpha than IL-10 secretion. In cells from nonatopic donors, glucocorticoids inhibited the production of TNF-alpha to a greater extent than IL-10, but these drugs were more potent in cells from nonatopic than atopic persons. Conclusion: In conclusion, both PDE-4 inhibitors and glucocorticoids suppress secretion of TNF-alpha and IL-10, However, because PDE-4 inhibitors are more potent in suppressing cytokine secretion by PBMCs from atopic individuals hut less potent in inhibiting production of IL-10, PDE-4 inhibitors may have greater therapeutic potential than glucocorticoids in allergic diseases.