Down-regulating effects of IL-4 and IL-10 on the IFN-gamma response in atopic dermatitis

Details

Serval ID
serval:BIB_C434471C74C9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Down-regulating effects of IL-4 and IL-10 on the IFN-gamma response in atopic dermatitis
Journal
Journal of Immunology
Author(s)
Lester  M. R., Hofer  M. F., Gately  M., Trumble  A., Leung  D. Y.
ISSN
0022-1767
Publication state
Published
Issued date
06/1995
Peer-reviewed
Oui
Volume
154
Number
11
Pages
6174-81
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jun 1
Abstract
Atopic dermatitis (AD) is a chronic allergic disease associated with toxin (superantigen)-producing Staphylococcus aureus skin infections, impaired delayed hypersensitivity responses, and the expansion of IL-4-secreting Th2 cells, as well as diminished IFN-gamma synthesis. IL-12 is known to induce IFN-gamma synthesis and to augment Th1 responses. In this study, therefore, we examined the potential role of IL-12 in the immunopathogenesis of AD. We show that, after stimulation with staphylococcal toxic shock syndrome toxin-1 (TSST-1) or IL-12, PBMC from patients with AD are deficient in their ability to produce IFN-gamma. PBMC from AD patients, however, produced normal quantities of IL-12 and expressed normal levels of IL-12R. Induction of IFN-gamma by TSST-1 was decreased by neutralizing anti-IL-12 Ab in normal donors, but not in AD patients. The latter observation is consistent with a defective response to IL-12 in AD PBMC. Because AD is associated with increased production of IL-4 and IL-10, we examined the effect of IL-4 on IL-12- or TSST-1-induced IFN-gamma production in normal donors. IL-4 inhibited IL-12-induced IFN-gamma production. Furthermore, Ab neutralization of IL-4 caused increased production of IFN-gamma in AD PBMC. However, neutralization of IL-10 activity caused an even greater augmentation of IFN-gamma production. Our data suggest that despite normal levels of IL-12 production and IL-12R expression, PBMC from AD patients are unable to generate normal IL-12-induced IFN-gamma responses. This defective response may be due to the excess production of IL-4 and IL-10 in this common allergic condition.
Keywords
Adolescent Adult Aged *Bacterial Toxins Cells, Cultured Dermatitis, Atopic/*immunology Down-Regulation/immunology Enterotoxins/immunology Humans Interferon Type II/*biosynthesis Interleukin-10/*physiology Interleukin-12/physiology Interleukin-4/*physiology Middle Aged Phytohemagglutinins/pharmacology Receptors, Interleukin/analysis Receptors, Interleukin-12 *Superantigens T-Lymphocytes/immunology
Pubmed
Web of science
Create date
20/01/2008 15:22
Last modification date
20/08/2019 15:39
Usage data