Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE) inhibitors in allergen-specific human T lymphocyte clones

Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical pharmacology 1997-04, Vol.53 (7), p.1055-1060
Main Authors: Essayan, David M., Kagey-Sobotka, Anne, Lichtenstein, Lawrence M., Hnang, Shau-Ku
Format: Article
Language:English
Subjects:
3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors
Allergens
allergy
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
cAMP
Clone Cells
Gene Expression
Glycoproteins - pharmacology
Guanidines - pharmacology
human
Humans
interleukin-13
Interleukin-13 - biosynthesis
Interleukin-13 - genetics
Lymphocyte Activation
Lymphocytes - drug effects
Lymphocytes - immunology
Medical sciences
Pharmacology. Drug treatments
phosphodiesterase
Phosphodiesterase Inhibitors - pharmacology
Pyridazines - pharmacology
Pyrrolidinones - pharmacology
Rolipram
T lymphocyte
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL-13 expression by cyclic nucleotide phosphodiesterase (PDE) inhibitors in a panel of Amb a 1 (a major allergen of short ragweed, Ambrosia artemisiifolia)-specific T cell clones derived from a ragweed allergic, asthmatic subject. Proliferative responses of these cells were down-regulated by rolipram, a PDE4 inhibitor (% inhibition max = 67%; IC 50 = 20 μM). While the PDE3 inhibitor siguazodan provided no independent efficacy ( IC 50 > 10 −4 M), an increased efficacy of rolipram in the presence of 10 −5 M siguazodan was noted at 10 −6, 10 −5, and 10 −4 M rolipram (P < 0.03, 0.01, and 0.04, respectively). The EC 50 values remained unchanged between assays using the PDE4 inhibitor with or without the PDE3 inhibitor. Both IL-13 gene expression and protein secretion into culture supernatants were down-regulated by the PDE4 inhibitor (P ⩽ 0.005). Once again, the use of a PDE3 inhibitor provided no independent efficacy (P ⩾ 0.2), and in this instance, increased efficacy of the PDE4 inhibitor with the PDE3 inhibitor was not apparent (P ⩾ 0.3). IL-13 production from clones with Th0, Th1, and Th2 phenotypes appeared equally sensitive to treatment with the PDE4 inhibitor. We conclude that the anti-inflammatory effects of PDE4 inhibitors may be mediated, in part, by down-regulation of IL-13.
ISSN:0006-2952
1873-2968
DOI:10.1016/S0006-2952(97)00102-0