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 t his study se compared the effect of glucocorticoids and PDE inhibitors on IL-10 and TNF-alpha production by PBMCs from nonatopic versus atop ic individuals. Methods: PBMCs were incubated with glucocorticoids (be clomethasone dipropionate and mometasone furoate) or media alone for 2 4 hours. PDE type 4 inhibitors (Ro20-1724 and rolipram) were then adde d to the cells preincubated with media. After stimulation with PHA, in cubation was continued for 48 hours, The cytokine content of the cell supernatants was determined by ELISA. Results: PDE-4 inhibitors and gl ucocorticoids caused a concentration-dependent inhibition of the secre tion of both TNF-alpha and IL-10. PDE-4 inhibitors were over 20 times more potent in suppressing cytokine secretion by PBMCs from atopic tha n nonatopic donors, and approximately 5 times more potent in preventin g TNF-alpha than IL-10 secretion. In cells from nonatopic donors, gluc ocorticoids inhibited the production of TNF-alpha to a greater extent than IL-10, but these drugs were more potent in cells from nonatopic t han atopic persons. Conclusion: In conclusion, both PDE-4 inhibitors a nd glucocorticoids suppress secretion of TNF-alpha and IL-10, However, because PDE-4 inhibitors are more potent in suppressing cytokine secr etion by PBMCs from atopic individuals hut less potent in inhibiting p roduction of IL-10, PDE-4 inhibitors may have greater therapeutic pote ntial than glucocorticoids in allergic diseases.