Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis

Jon Hanifin, Sai C. Chan, John B. Cheng, Susan Tofte, William R. Henderson, Deborah S. Kirby, Ethan S. Weiner

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

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 h 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 antiinflammatory efficacy may provide a useful alternative to the over-reliance on corticosteroid therapy in atopic disease.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalJournal of Investigative Dermatology
Volume107
Issue number1
StatePublished - 1996

Fingerprint

Phosphodiesterase 4 Inhibitors
Atopic Dermatitis
Phosphodiesterase Inhibitors
Anti-Inflammatory Agents
Interleukin-10
Mononuclear Leukocytes
Matched-Pair Analysis
Assays
Phosphoric Diester Hydrolases
Dinoprostone
Interleukin-4
Leukocytes
Enzyme activity
Enzyme Inhibitors
Ointments
Immunoassay
Cyclic AMP
Skin
Adrenal Cortex Hormones
Blood

Keywords

  • IL-10
  • Monocytes
  • PDE/IL-4

ASJC Scopus subject areas

  • Dermatology

Cite this

Hanifin, J., Chan, S. C., Cheng, J. B., Tofte, S., Henderson, W. R., Kirby, D. S., & Weiner, E. S. (1996). Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. Journal of Investigative Dermatology, 107(1), 51-56.

Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. / Hanifin, Jon; Chan, Sai C.; Cheng, John B.; Tofte, Susan; Henderson, William R.; Kirby, Deborah S.; Weiner, Ethan S.

In: Journal of Investigative Dermatology, Vol. 107, No. 1, 1996, p. 51-56.

Research output: Contribution to journalArticle

Hanifin, J, Chan, SC, Cheng, JB, Tofte, S, Henderson, WR, Kirby, DS & Weiner, ES 1996, 'Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis', Journal of Investigative Dermatology, vol. 107, no. 1, pp. 51-56.
Hanifin, Jon ; Chan, Sai C. ; Cheng, John B. ; Tofte, Susan ; Henderson, William R. ; Kirby, Deborah S. ; Weiner, Ethan S. / Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. In: Journal of Investigative Dermatology. 1996 ; Vol. 107, No. 1. pp. 51-56.
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