title: gamma-interferon production in atopic dermatitis shows differential modification by phosphodiesterase and prostaglandin inhibition.
abstract: Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear leucocytes (MNL) is reduced in atopic dermatitis (AD) patients. This may be related to abnormalities in second messenger systems, and increased prostaglandin E2 (PGE2) release from monocytes. We compared the effects of manipulating the second messenger activity using the phosphodiesterase (PDE) inhibitor Ro 20-1724, dibutyryl cyclic adenosine monophosphate (cAMP), and cyclooxygenase inhibition of PGE2, on IFN-gamma production by cultured MNL from AD patients (n = 9) and normal controls (n = 10). Ficoll-Hypaque-separated MNL were cultured for 48 h with OKT3 stimulation, and cAMP, Ro 20-1724, or indomethacin. Supernatants were analysed for IFN-gamma by ELISA. Basal IFN-gamma was lower in AD patients, and the increase in IFN-gamma production with OKT3 was 6.5-fold greater in control subjects than patients with AD. Culture with indomethacin significantly enhanced OKT3-stimulated IFN-gamma production in both groups, whereas OKT3-stimulated IFN-gamma production was abolished with dibutyryl cAMP. IFN-gamma production was significantly lower with Ro 20-1742 in AD than in normal controls. We have shown reduced IFN-gamma release from unstimulated and stimulated MNL in AD patients compared with normal controls. The addition of indomethacin increased IFN-gamma production in both groups, although the increase was less in AD patients, suggesting an intrinsic cellular defect. IFN-gamma release from AD MNL was more sensitive to the inhibitory effects of PDE, and this may be due to increased PDE activity, or the hyperdynamic cAMP system present in atopics.
authors.affiliation: Department of Dermatology, St Helier NHS Trust, Carshalton, Surrey, U.K.
authors.forename: L S
authors.initials: LS
authors.lastname: Ostlere
authors.forename: R B
authors.initials: RB
authors.lastname: Mallett
authors.forename: A
authors.initials: A
authors.lastname: Kaminski
authors.forename: E R
authors.initials: ER
authors.lastname: Kaminski
authors.forename: R S
authors.initials: RS
authors.lastname: Pereira
authors.forename: C A
authors.initials: CA
authors.lastname: Holden
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000378:metabolism*; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; C048819:4-(3,4-dibutoxybenzyl)-2-imidazolidinone; D003994:Bucladesine; D007371:Interferon-gamma; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015232:Dinoprostone; D007213:Indomethacin