Increased interleukin-4 production by atopic mononuclear leukocytes correlates with increased cyclic adenosine monophosphate-phosphodiesterase activity and is reversible by phosphodiesterase inhibition

Sai C. Chan, Shi Hua Li, Jon Hanifin

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Abstract

Previous studies have shown that leukocytes from patients with atopic dermatitis have increased levels of cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity. This increased activity accounts for subnormal cAMP responses and correlates with increased in vitro immunoglobulin E production. To better understand the mechanism of this effect, we studied the relationship between phosphodiesterase activity and interleukin-4, a T-cell-derived cytokine that is a major regulator of immunoglobulin E production. Cultures stimulated with anti-CD3 or with phorbol myristate acetate plus ionophore significantly increased interleukin-4 production, and levels were consistently highest in cells from atopic subjects. Interleukin-4 production was higher, on a per T-cell basis, in mononuclear leukocyte cultures than in cultures of pure T cells, suggesting the possibility of a monocyte factor acting to increase interleukin-4 production. We next examined the effect of the phosphodiesterase inhibitor Ro 20-1724 on interleukin-4 production and found a significant reduction in cultures of atopic mononuclear leukocytes. This phosphodiesterase inhibitor effect appeared to act primarily on monocytes and correlated with increased intracellular cAMP levels. These studies demonstrate increased interleukin-4 production by atopic T cells. This abnormality can be reversed by inhibition of cAMP-phosphodiesterase, suggesting a possible therapeutic target for control of atopic disease.

Original languageEnglish (US)
Pages (from-to)681-684
Number of pages4
JournalJournal of Investigative Dermatology
Volume100
Issue number5
StatePublished - May 1993

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Mononuclear Leukocytes
Phosphoric Diester Hydrolases
Interleukin-4
Cyclic AMP
T-cells
T-Lymphocytes
Phosphodiesterase Inhibitors
Immunoglobulin E
Monocytes
Cell culture
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
Ionophores
Tetradecanoylphorbol Acetate
Atopic Dermatitis
Leukocytes
Cytokines

ASJC Scopus subject areas

  • Dermatology

Cite this

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title = "Increased interleukin-4 production by atopic mononuclear leukocytes correlates with increased cyclic adenosine monophosphate-phosphodiesterase activity and is reversible by phosphodiesterase inhibition",
abstract = "Previous studies have shown that leukocytes from patients with atopic dermatitis have increased levels of cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity. This increased activity accounts for subnormal cAMP responses and correlates with increased in vitro immunoglobulin E production. To better understand the mechanism of this effect, we studied the relationship between phosphodiesterase activity and interleukin-4, a T-cell-derived cytokine that is a major regulator of immunoglobulin E production. Cultures stimulated with anti-CD3 or with phorbol myristate acetate plus ionophore significantly increased interleukin-4 production, and levels were consistently highest in cells from atopic subjects. Interleukin-4 production was higher, on a per T-cell basis, in mononuclear leukocyte cultures than in cultures of pure T cells, suggesting the possibility of a monocyte factor acting to increase interleukin-4 production. We next examined the effect of the phosphodiesterase inhibitor Ro 20-1724 on interleukin-4 production and found a significant reduction in cultures of atopic mononuclear leukocytes. This phosphodiesterase inhibitor effect appeared to act primarily on monocytes and correlated with increased intracellular cAMP levels. These studies demonstrate increased interleukin-4 production by atopic T cells. This abnormality can be reversed by inhibition of cAMP-phosphodiesterase, suggesting a possible therapeutic target for control of atopic disease.",
author = "Chan, {Sai C.} and Li, {Shi Hua} and Jon Hanifin",
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AU - Li, Shi Hua

AU - Hanifin, Jon

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N2 - Previous studies have shown that leukocytes from patients with atopic dermatitis have increased levels of cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity. This increased activity accounts for subnormal cAMP responses and correlates with increased in vitro immunoglobulin E production. To better understand the mechanism of this effect, we studied the relationship between phosphodiesterase activity and interleukin-4, a T-cell-derived cytokine that is a major regulator of immunoglobulin E production. Cultures stimulated with anti-CD3 or with phorbol myristate acetate plus ionophore significantly increased interleukin-4 production, and levels were consistently highest in cells from atopic subjects. Interleukin-4 production was higher, on a per T-cell basis, in mononuclear leukocyte cultures than in cultures of pure T cells, suggesting the possibility of a monocyte factor acting to increase interleukin-4 production. We next examined the effect of the phosphodiesterase inhibitor Ro 20-1724 on interleukin-4 production and found a significant reduction in cultures of atopic mononuclear leukocytes. This phosphodiesterase inhibitor effect appeared to act primarily on monocytes and correlated with increased intracellular cAMP levels. These studies demonstrate increased interleukin-4 production by atopic T cells. This abnormality can be reversed by inhibition of cAMP-phosphodiesterase, suggesting a possible therapeutic target for control of atopic disease.

AB - Previous studies have shown that leukocytes from patients with atopic dermatitis have increased levels of cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity. This increased activity accounts for subnormal cAMP responses and correlates with increased in vitro immunoglobulin E production. To better understand the mechanism of this effect, we studied the relationship between phosphodiesterase activity and interleukin-4, a T-cell-derived cytokine that is a major regulator of immunoglobulin E production. Cultures stimulated with anti-CD3 or with phorbol myristate acetate plus ionophore significantly increased interleukin-4 production, and levels were consistently highest in cells from atopic subjects. Interleukin-4 production was higher, on a per T-cell basis, in mononuclear leukocyte cultures than in cultures of pure T cells, suggesting the possibility of a monocyte factor acting to increase interleukin-4 production. We next examined the effect of the phosphodiesterase inhibitor Ro 20-1724 on interleukin-4 production and found a significant reduction in cultures of atopic mononuclear leukocytes. This phosphodiesterase inhibitor effect appeared to act primarily on monocytes and correlated with increased intracellular cAMP levels. These studies demonstrate increased interleukin-4 production by atopic T cells. This abnormality can be reversed by inhibition of cAMP-phosphodiesterase, suggesting a possible therapeutic target for control of atopic disease.

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