Modulation of allergic responses in mice by using biodegradable poly(lactide-co-glycolide) microspheres.

Details

Serval ID
serval:BIB_C256D20180EB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Modulation of allergic responses in mice by using biodegradable poly(lactide-co-glycolide) microspheres.
Journal
Journal of Allergy and Clinical Immunology
Author(s)
Jilek S., Walter E., Merkle H.P., Corthésy B.
ISSN
0091-6749[print], 0091-6749[linking]
Publication state
Published
Issued date
2004
Volume
114
Number
4
Pages
943-950
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
BACKGROUND: Biodegradable poly(lactide- co -glycolide) (PLGA) microspheres are a promising carrier for vaccine delivery capable of maturing antigen-presenting cells to stimulate T-cell-mediated immune responses. However, the potential of microspheres to downregulate an allergic response in vivo is unknown. OBJECTIVE: The aim of this study was to determine whether microspheres could potentiate DNA vaccination against allergy and to evaluate the immunomodulatory properties of microspheres alone. METHODS: Mice were treated prophylactically with DNA-loaded plain PLGA microspheres before sensitization with phospholipase A2 (PLA2), the major allergen of bee venom. PLA2-specific IgG1, IgG2a, IgE in serum were measured for 8.5 months, and splenocyte proliferative responses and cytokine profiles were determined. Protection against anaphylaxis was evaluated after injection of an otherwise lethal dose of PLA2. RESULTS: Phospholipase A2-specific IgG1 and IgG2a production turned out to be 2 times higher using cationic microspheres compared with anionic microspheres, but was not influenced by the presence of DNA. In contrast, reduction in IgE production and T-cell hyporesponsiveness were observed with all microsphere formulations. Recall challenge with PLA2 triggered combined expression of both IL-4 and IFN-gamma, together with sustained expression of IL-10 that can explain the protective effect against anaphylaxis. CONCLUSION: Our data suggest a dual mechanism that does initially rely on a TH2 to TH1 immune deviation and then on IL-10-mediated suppression. This is the first physiological demonstration that plain PLGA microspheres can induce tolerance in mice for as long as 6 months postsensitization.
Keywords
Absorbable Implants, Animals, Bee Venoms/immunology, Biocompatible Materials/administration & dosage, Drug Carriers, Hypersensitivity/immunology, Hypersensitivity/therapy, Injections, Subcutaneous, Interleukin-10/immunology, Mice, Microspheres, Models, Animal, Phospholipases A/immunology, Phospholipases A2, Polyglactin 910/administration & dosage, T-Lymphocytes/immunology, Vaccination/instrumentation, Vaccines, DNA/administration & dosage
Pubmed
Web of science
Create date
25/01/2008 15:53
Last modification date
20/08/2019 16:37
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