TY - JOUR
T1 - Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors
AU - Crocker, I. Caroline
AU - Ohia, S. Edet
AU - Church, Martin K.
AU - Townley, Robert G.
PY - 1998/1/1
Y1 - 1998/1/1
N2 - Background: Both glucocorticosteroids and phosphodiesterase (PDE) type 4 inhibitors have modulatory effects on PBMC cytokine secretion. In this study we compared the effect of glucocorticoids and PDE inhibitors on IL-10 and TNF-α 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-α 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-α than IL-10 secretion. In cells from nonatopic donors, glucocorticoids inhibited the production of TNF-α 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-α and IL-10. However, because PDE-4 inhibitors are more potent in suppressing cytokine secretion by PBMCs from atopic individuals but less potent in inhibiting production of IL-10, PDE-4 inhibitors may have greater therapeutic potential than glucocorticoids in allergic diseases.
AB - Background: Both glucocorticosteroids and phosphodiesterase (PDE) type 4 inhibitors have modulatory effects on PBMC cytokine secretion. In this study we compared the effect of glucocorticoids and PDE inhibitors on IL-10 and TNF-α 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-α 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-α than IL-10 secretion. In cells from nonatopic donors, glucocorticoids inhibited the production of TNF-α 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-α and IL-10. However, because PDE-4 inhibitors are more potent in suppressing cytokine secretion by PBMCs from atopic individuals but less potent in inhibiting production of IL-10, PDE-4 inhibitors may have greater therapeutic potential than glucocorticoids in allergic diseases.
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U2 - 10.1016/S0091-6749(98)70020-X
DO - 10.1016/S0091-6749(98)70020-X
M3 - Article
C2 - 9819297
AN - SCOPUS:0031753056
VL - 102
SP - 797
EP - 804
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 5
ER -