Impacto do transtorno depressivo maior no perfil fenotípico e funcional das células T CD4+ em pacientes com asma e rinite alérgica

Abstract

The Major Depressive Disorder (MDD) may impact in the severity of Allergic Rhinitis (AR) and Asthma (AA), two disorders related to the expansion of allergen-specific effector T CD4+ cells that are associated with impairment of immune regulatory mechanisms. The cellular structure behind this adverse relationship aren’t know, but may involve disbalance in the cytokine network and serotonin (5-HT) production, a neurotransmitter capable of modulating T cell functions. As such, the objective of this study was to evaluate, in vitro, the production of cytokines by T cells of patients with AR and AA, that may or may not have MDD. The effects of 5-HT in T cell response was also analyzed. To do so, peripheric blood mononuclear cells cultures were activated with Phorbol 12-myristate 13-acetate (PMA) and Ionomycin, for 4h, or with magnetic beads covered in anti-CD3 and anti-CD28 antibodies, for 72h. Cytokine production was measured by Luminex and flow cytometry. Cell proliferation was determined by [3H] thymidine incorporation. 5-HT was added to some cell cultures. Our results show that, despite no significant changes in cell proliferation, MDD enhanced not only the production of cytokines related to the Th2 and Th17 phenotypes, but also a direct correlation between IL-5 and IL-17 levels and the severity of depressive and anxious symptoms. Cultures from AA patients, when compared to AR individuals, presented higher levels IL-17 and lower production of IL-10, specially in those with MDD. In AA/MDD individuals, the severity of anxious symptoms and pulmonary disease was directly correlated with Th17 and Th2/Th17 frequencies, but inversely correlated with T CD4+IL-10+ frequencies. Moreover, 5-HT supplementation in cultures of AA and RA individuals was capable of reducing the production of cytokines related to Th2 and Th17 phenotypes, while increasing IL-10 release. Although preliminarily, our findings suggest that, not only MDD, but also the severity of the disorder may negatively impact the outcome of allergic reactions by enhancing the production of cytokines associated with AA and AR pathogenesis, with such phenomenon being attenuated by serotonin