Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating T_reg and T_h 17 Cells

Abstract

The first two authors contributed equally to this work 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.) ofAR were evaluated to determine the severity ofAR. Cytokines in the nasal lavage fluid (NALF), including interferon-y (IFN-y), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (T reg ) and T helper cells 17 (Thl7) 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-y level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+T reg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+T h17 cells, which were significantly increased inAR 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 T reg 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.

Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy

“…Himmerich et al (2010) described a similar increase in T reg cells in a naturalistic study of antidepressant treatment in 16 MDD patients. Moreover, desipramine treatment increased T reg cells in a mouse model of allergic rhinitis (Zhang et al 2013). It is thus possible that antidepressants, and in particular tricyclic antidepressants, facilitate the normalization of inflammatory activation in MDD patients by increasing the T reg cell population.…”

Old Friends, immunoregulation, and stress resilience

“…For instance, individuals with inflammatory diseases are three to four times more likely to experience depression [69, 99, 103, 254, 441]. Moreover, although low-dose intravenous injection of Salmonella abortus equi endotoxin (0.8 ng/kg body weight) had no effects on physical sickness symptoms, blood pressure or heart rate, elevation of circulating cytokine levels (TNF, soluble TNF receptors, IL-6, IL-1 receptor antagonist) was positively correlated with endotoxin-induced anxiety levels and depressed mood and negatively correlated with verbal and non-verbal memory functions [339].…”

Regulatory T Cells as Immunotherapy

“…Generation of IL-10-producing Tregs may be a prominent mechanism underlying these findings (15). The antidepressant drug desipramine appears to alleviate allergic rhinitis by regulating Tregs and Th17 cells (120). Although clinical trials have not attempted adoptive transfer of Tregs for allergic disease, protocols to expand allergen-specific Tregs may potentially benefit atopic patients.…”