title: Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors.
abstract: 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-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.
  
  
  CONCLUSIONS
  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 but less potent in inhibiting production of IL-10, PDE-4 inhibitors may have greater therapeutic potential than glucocorticoids in allergic diseases.
authors.affiliation: Department of Medicine/Division of Allergy, Creighton University, Omaha, NE 68178, USA.
authors.forename: I C
authors.initials: IC
authors.lastname: Crocker
authors.forename: S E
authors.initials: SE
authors.lastname: Ohia
authors.forename: M K
authors.initials: MK
authors.lastname: Church
authors.forename: R G
authors.initials: RG
authors.lastname: Townley
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000293:Adolescent; D000328:Adult; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood*; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D013755:Tetradecanoylphorbol Acetate