Increased leukocyte sensitivity to phosphodiesterase inhibitors in atopic dermatitis

Tachyphylaxis after theophylline therapy

Thomas A. Giustina, Sai C. Chan, Marcella L. Thiel, James W. Baker, Jon Hanifin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Previous studies have demonstrated elevated cyclic 3′,5′-adenosine monophosphate specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD) and with allergic respiratory disease. We have studied the effect of PDE inhibitors on MNL from normal subjects and from patients with AD. We measured PDE activity in MNL after in vitro exposure to Ro20-1724, theophylline, and isobutylmethylxanthine. The effect of PDE inhibitors was also measured in MNL of patients during and after oral theophylline therapy. There was a dose-response effect of Ro20-1724 on PDE activity of AD cells. This activity was significantly more inhibited than that in MNL of normal subjects or in MNL of theophylline-treated patients with AD. The inhibition pattern of PDE in MNL of treated patients with AD did not vary significantly from the pattern observed in MNL from normal patients. Two weeks after oral theophylline was stopped, the PDE activity in MNL was once again susceptible to in vitro inhibition. The relative resistance of MNL to PDE activity in normal subjects to in vitro PDE inhibitors may be due to the existence of different PDE enzyme forms or the presence of endogenous inhibitors. The clinical importance of the tachyphylaxis observed is uncertain, but our results suggest that intermittent dosing with PDE inhibitors may provide a therapeutic advantage in treatment of AD and other atopic diseases.

Original languageEnglish (US)
Pages (from-to)252-257
Number of pages6
JournalThe Journal of allergy and clinical immunology
Volume74
Issue number3 PART 1
DOIs
StatePublished - 1984

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Tachyphylaxis
Mononuclear Leukocytes
Phosphodiesterase Inhibitors
Atopic Dermatitis
Theophylline
Leukocytes
Phosphoric Diester Hydrolases
Therapeutics
Adenosine Monophosphate

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Increased leukocyte sensitivity to phosphodiesterase inhibitors in atopic dermatitis : Tachyphylaxis after theophylline therapy. / Giustina, Thomas A.; Chan, Sai C.; Thiel, Marcella L.; Baker, James W.; Hanifin, Jon.

In: The Journal of allergy and clinical immunology, Vol. 74, No. 3 PART 1, 1984, p. 252-257.

Research output: Contribution to journalArticle

Giustina, Thomas A. ; Chan, Sai C. ; Thiel, Marcella L. ; Baker, James W. ; Hanifin, Jon. / Increased leukocyte sensitivity to phosphodiesterase inhibitors in atopic dermatitis : Tachyphylaxis after theophylline therapy. In: The Journal of allergy and clinical immunology. 1984 ; Vol. 74, No. 3 PART 1. pp. 252-257.
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