GAMMA-INTERFERON PRODUCTION IN ATOPIC-DERMATITIS SHOWS DIFFERENTIAL MODIFICATION BY PHOSPHODIESTERASE AND PROSTAGLANDIN INHIBITION

Interferon-gamma (IFN-gamma) production by peripheral blood mononuclea r leucocytes (MNL) is reduced in atopic dermatitis (AD) patients. This may be related to abnormalities in second messenger systems, and incr eased prostaglandin E(2) (PGE(2)) release from monocytes. We compared the effects of manipulating the second messenger activity using the ph osphodiesterase (PDE) inhibitor Ro 20-1724, dibutyryl cyclic adenosine monophosphate (cAMP), and cyclooxygenase inhibition of PGE(2), on IFN -gamma production by cultured MNL from AD patients (n=9) and normal co ntrols (n=10). Ficoll-Hypaque-separated MNL were cultured for 48 h wit h OKT3 stimulation, and cAMP, Ro 20-1724, or indomethacin. Supernatant s were analysed for IFN-gamma by ELISA. Basal IFN-gamma was lower in A D 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 producti on in both groups, whereas OKT3-stimulated IFN-gamma production was ab olished with dibutyryl cAMP. IFN-gamma production was significantly lo wer with Ro 20-1742 in AD than in normal controls. We have shown reduc ed IFN-gamma release from unstimulated and stimulated MNL in AD patien ts compared with normal controls. The addition of indomethacin increas ed IFN-gamma production in both groups, although the increase was less in AD patients, suggesting an intrinsic cellular defect. IFN-gamma re lease from AD MNL was more sensitive to the inhibitory effects of PDE, and this may be due to increased PDE activity, or the hyperdynamic cA MP system present in atopics.