title: Antidepressant drug, desipramine, alleviates allergic rhinitis by regulating Treg and Th17 cells.
abstract: Allergic rhinitis (AR) is characterized by IgE-mediated immediate hypersensitivity and usually progresses to chronic nasal inflammation, with depression as one of its comorbidities. The importance of treating the depression in AR patients has been increasingly recognized. Desipramine is a representative of tricyclic-antidepressant agents. In the present study we investigate whether desipramine has therapeutic effects on AR inflammation. BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by repeated challenge with OVA intranasally. Desipramine was administered orally to treat the mice. The nasal symptoms (sneezing, nasal scratching etc.) of AR were evaluated to determine the severity of AR. Cytokines in the nasal lavage fluid (NALF), including interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (Treg) and T helper cells 17 (Th17) were quantified by flow cytometric analysis. As a result, the repeated oral administration of desipramine attenuated the nasal symptoms (sneezing and nasal rubbing) in AR mice. Desipramine also suppressed the serum OVA-specific IgE and IL-4 levels, but had no effect on IFN-gamma level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+ Treg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+ Th17 cells, which were significantly increased in AR mice. These results suggest that the antidepressant drug, desipramine, also has anti-allergic action, which was possibly achieved by reducing allergen-specific IgE and Th2 cytokine production and maintaining a balance between Treg and Th17 cells. Thus, this study provide the first evidence that desipramine may be utilized to treat allergic diseases, especially for those allergic patients with depression or depression patients with allergy.
authors.affiliation: Department of Pharmacology, Huazhong University of Science and Technology, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Zhen
authors.forename: W
authors.initials: W
authors.lastname: Yao
authors.forename: F
authors.initials: F
authors.lastname: Bian
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Jin
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017817:Nasal Lavage Fluid / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D000928:Antidepressive Agents; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D003891:Desipramine