Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating Treg and Th 17 Cells
Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating Treg and Th 17 Cells
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DOI：
10.1177/039463201302600110
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发表时间：
2013-01
影响因子：
3.5
通讯作者：
Y. Zhang;H. Zhen;W. Yao;F. Bian;X. Mao;X. Yang;S. Jin
中科院分区：
文献类型：
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作者：
Y. Zhang;H. Zhen;W. Yao;F. Bian;X. Mao;X. Yang;S. Jin
变应性鼻炎(AR)以IgE介导的即刻超敏反应为特征，通常进展为慢性鼻炎，抑郁是其共病之一。人们越来越认识到治疗AR患者抑郁的重要性。地塞帕明是三环类抗抑郁药的代表。在本研究中，我们研究了地塞帕明是否对AR炎症有治疗作用。给BALB/C小鼠腹腔注射卵白蛋白(OVA)致敏，然后用OVA反复鼻腔激发。口服地昔帕明治疗小鼠。鼻部症状(打喷嚏、鼻痒等)对AR进行评估以确定AR的严重程度。用双抗体夹心法检测鼻腔灌洗液中细胞因子干扰素-γ(干扰素-γ)、白介素4(IL-4)和血清卵清蛋白特异性免疫球蛋白E抗体。用流式细胞仪分析调节性T细胞(Treg)和辅助性T细胞17(Th17)的数量。结果，反复口服地昔帕明减轻了AR小鼠的鼻部症状(打喷嚏和鼻部摩擦)。地塞帕明也能抑制血清卵清蛋白特异性Ig E和IL-4水平，但对干扰素-γ水平无影响。此外，地塞帕明治疗上调了CD4+CD25+Foxp3+Treg细胞，而在已建立的AR小鼠中发现这些细胞下调。同时，给予地昔帕明后，AR小鼠外周血中的CD4+IL-17+Th17细胞显著增加。这些结果表明，抗抑郁药物地昔帕明也有抗过敏作用，这可能是通过减少过敏原特异性IgE和Th2细胞因子的产生，以及维持Treg和Th17细胞之间的平衡来实现的。因此，本研究首次提供了地昔帕明可用于治疗过敏性疾病的证据，特别是对那些伴有抑郁的过敏性患者或伴有变态反应的抑郁症患者。
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-γ (IFN-γ), 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-γ 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.