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Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis In Mice

Posted on:2013-05-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2234330392456602Subject:Department of Otolaryngology Head and Neck Surgery
Abstract/Summary:PDF Full Text Request
Background: Desipramine belongs to tricyclic-antidepressant drug and was alsoreported to have an inhibiting activity on acid sphingomyelinas, which wasdemonstrated to play essential roles in inflammation. Allergic rhinitis (AR) is causedby IgE-mediated immediate hypersensitivity and ultimately progresses as chronicnasal inflammation. The present study was designed to investigate whetherdesipramine has treatment effects on nasal symptoms of allergic rhinitis model inmice.Materials and Methods: BALB/C mice were sensitized by intraperitoneal injectionof ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum), followed byrepeated challenge with OVA intranasally. Desipramine was administered orally aftereach instillation of OVA. The multiple aspects (sneezing, scraching etc.) of allergicresponses were evaluated to determine the severity of the mice’s sickness. SerumOVA-specific immunoglobulin E (IgE) levels and interleukin4(IL-4), INF-γ, in nasallavage fluid were measured by ELISA kits respectively to determine theallergy-related cytokines. The numbers of regulated T cells (Treg) and IL-17cells(Th17) were counted by flow cytometry analysis to investigate the mechanisminvolved.Results: Repeated oral administration of desipramine attenuated the progression ofnasal symptoms—sneezing and nasal rubbing in sensitized mice in a dose-dependentmanner. It also suppressed serum OVA-specific immunoglobulin E (IgE) levels andinterleukin4(IL-4) in nasal lavage fluid; however, it had no effect on INF-γ levels inlavage fluid. Moreover, desipramine treatment inhibited the airway inflammation ofallergic rhinitis by regulating the balance between Treg and Th17.Conclusion: These results demonstrate that desipramine has the characteristic ofanti-allergic effect by reducing OVA-specific IgE and IL-4levels, and moduating theratio of spleen CD4+CD25+Foxp3+cell and CD4+IL-17+cells. Basides the theory of Th1/Th2equilibrum, the balance of Treg/Th17can also play a role in the pathogenesisof allergic rhinitis, which provide a new theoretical foundation for the further study.Therefore, desipramine should have potential in the development of therapies forallergic rhinitis.
Keywords/Search Tags:desipramine, allergic rhinitis, Immumoglobulin E, Interleukin-4, Interferon-gamma, Treg, TH17
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