Modulation of allergic responses in mice by using biodegradable poly(lactide-co-glycolide) microspheres - 25/08/11
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Zurich and Lausanne, Switzerland
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-γ, 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.
Le texte complet de cet article est disponible en PDF.Key words : Allergy, microspheres, TH1/TH2 responses, immunomodulation
Abbreviations used : DC, EV, PLGA, PLA2, PLA2V, SI
Plan
Supported by grants from the Swiss National Research Foundation (grants NFP 4037-55144 to Dr Merkle and 3200-068038 to Dr Corthésy) and the Huber-Kudlich Foundation from the Swiss Federal Institute of Technology, Zurich (grant 02409/41-2315.5). |
Vol 114 - N° 4
P. 943-950 - octobre 2004 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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