Increased
cyclic AMP-
phosphodiesterase activity in peripheral blood leukocytes is associated with the immune and inflammatory hyperreactivity that characterizes
atopic dermatitis. Atopic
phosphodiesterase has high sensitivity to a variety of
enzyme inhibitors, suggesting an increased therapeutic advantage. The objective of this study was to use in vitro assays to identify a potent
phosphodiesterase inhibitor and then to investigate its effectiveness in treating
atopic dermatitis. Leukocyte
enzyme activity was measured by radioenzyme assay, whereas
prostaglandin E2 and
interleukins 10 (IL-10) and 4 (IL-4) were measured in 24-h culture supernatants of mononuclear leukocytes by immunoassays. The effect of a topical
phosphodiesterase inhibitor on
atopic dermatitis lesional skin was assessed by double-blind, paired comparisons of active
drug and placebo
ointments applied to symmetrically involved sites over a 28-d period. Using in vitro, assays, we demonstrated the ability of selective high-potency
phosphodiesterase inhibitors to reduce
prostaglandin E2,
IL-10, and
IL-4 production in atopic mononuclear leukocyte cultures. We selected the Type 4
phosphodiesterase inhibitor, CP80,633, based on its inhibitory potency, for clinical testing by topical, bilateral paired comparisons in 20 patients with
atopic dermatitis and demonstrated significant reductions of all inflammatory parameters.
Phosphodiesterase inhibitors modulate several pathways contributing to the exaggerated immune and inflammatory responses, which characterize
atopic dermatitis. This in vivo demonstration of anti-inflammatory efficacy may provide a useful alternative to the over-reliance on
corticosteroid therapy in atopic disease.