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- Title
Gamma -- interferon production in atopic dermatitis shows differential modification by phosphodiesterase and prostaglandin inhibition.
- Authors
Ostlere, L. S.; Mallett, R. B.; Kaminski, A.; Kaminski, E. R.; Pereira, R. S.; Holden, C. A.
- Abstract
Interferon-gamma (IEN-γ) 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 IEN-γ production by cultured MNL from AD patients (n=9) and normal controls (n=10). FicollHypaque-separated MNL were cultured for 48 h with 0KT3 stimulation, and cAMP, Ro 20– 1724, or indomethacin. Supernatants were analysed for IFN-γ by ELISA. Basal IFN-γ was lower in AD patients, and the increase in IFN-γ production with OKT3 was 6-5-fold greater in control subjects than patients with AD. Culture with indomethacin significantly enhanced 0KT3-stimulated IFN-γ production in both groups, whereas OKT3-stimulated IFN-γ production was abolished with dibutyryl cAMP. IFN-γ production was significantly lower with Ro 20–1742 in AD than in normal controls. We have shown reduced IFN-γ release from unstimulated and stimulated MNL in AD patients compared with normal controls. The addition of indomethacin increased IFN-γ production in both groups, although the increase was less in AD patients, suggesting an intrinsic cellular defect. IFN-γ 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.
- Subjects
INTERFERONS; ATOPIC dermatitis; SKIN inflammation; PHOSPHODIESTERASES; PROSTAGLANDINS; DERMATOLOGY
- Publication
British Journal of Dermatology, 1995, Vol 133, Issue 1, p1
- ISSN
0007-0963
- Publication type
Article
- DOI
10.1111/1365-2133.ep14842999