Análise de parâmetros imunológicos em mulheres com transtorno bipolar tipo I, eutímicas

Abstract

Bipolar Disorder (BD) is a complex, multifactorial and chronic psychiatic illness. It is characterized by alternating cycles of mania and depression, with periods of remission or euthymia. Several studies have suggested a direct interaction between nervous, endocrine and immune systems in the pathophysiology of BD. An immune activation, as evidenced by increased plasma levels of proinflammatory cytokines, has been frequently reported in BD. However, the majority of the studies have mainly investigated mania and depression phases, and very few studies have been developed with euthymic patients. In this study, we investigated cellular and molecular mechanisms potentially involved in the inflammatory process in BD, including various lymphocytes subtypes and intracelular pathways of lymphocyte activation. Twentyseven euthymic female subjects with BD type I and 24 age- and sex-matched controls were recruited in this study. Lymphocytes were isolated and stimulated in vitro to assess Th1/Th17/Th2 cytokines (IL-2, IL-4, IL-5, IL-10, IL-17, IFN-ע and TNF-æ) and expression of mitogen-activated protein kinases (MAPKs). The expression of MAPKs (p-oERK and p38), lymphocyte subtypes and cytokines were assessed by flow cytometry. All cytokines assessed were found elevated in bipolar disorder compared with healthy controls. In particu-lar, it was evidenced a bias to a Th1 inflammatory profile in BD. Interestingly, we observed a significant reduction (-56%) of regulatory T cells (CD4+CD25+Foxp3+) and expansion (43%) of CD8+ regulatory T cells (CD8+CD28-) in BD. The lymphocytes of BD patients showed an significant increase in p-ERK in relation to p-p38, indicating lymphocyte activation. Our data suggest that multiple molecular and cellular mechanisms contribute to the immunological imbalance observed in BD